Toward a comprehensive catalog of regulatory elements.
Journal
Human genetics
ISSN: 1432-1203
Titre abrégé: Hum Genet
Pays: Germany
ID NLM: 7613873
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
06
11
2022
accepted:
03
01
2023
medline:
25
8
2023
pubmed:
21
3
2023
entrez:
20
3
2023
Statut:
ppublish
Résumé
Regulatory elements are the genomic regions that interact with transcription factors to control cell-type-specific gene expression in different cellular environments. A precise and complete catalog of functional elements encoded by the human genome is key to understanding mammalian gene regulation. Here, we review the current state of regulatory element annotation. We first provide an overview of assays for characterizing functional elements, including genome, epigenome, transcriptome, three-dimensional chromatin interaction, and functional validation assays. We then discuss computational methods for defining regulatory elements, including peak-calling and other statistical modeling methods. Finally, we introduce several high-quality lists of regulatory element annotations and suggest potential future directions.
Identifiants
pubmed: 36935423
doi: 10.1007/s00439-023-02519-3
pii: 10.1007/s00439-023-02519-3
doi:
Substances chimiques
Chromatin
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1091-1111Subventions
Organisme : National Institute on Handicapped Research
ID : HG012343
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Akalin A, Fredman D, Arner E et al (2009) Transcriptional features of genomic regulatory blocks. Genome Biol 10:R38. https://doi.org/10.1186/gb-2009-10-4-r38
doi: 10.1186/gb-2009-10-4-r38
pubmed: 19374772
pmcid: 2688929
Alexander RP, Fang G, Rozowsky J et al (2010) Annotating non-coding regions of the genome. Nat Rev Genet 11:559–571. https://doi.org/10.1038/nrg2814
doi: 10.1038/nrg2814
pubmed: 20628352
Alipanahi B, Delong A, Weirauch MT, Frey BJ (2015) Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning. Nat Biotechnol 33:831–838. https://doi.org/10.1038/nbt.3300
doi: 10.1038/nbt.3300
pubmed: 26213851
Altarejos JY, Montminy M (2011) CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nat Rev Mol Cell Biol 12:141–151. https://doi.org/10.1038/nrm3072
doi: 10.1038/nrm3072
pubmed: 21346730
pmcid: 4324555
Andersson R, Sandelin A (2020) Determinants of enhancer and promoter activities of regulatory elements. Nat Rev Genet 21:71–87. https://doi.org/10.1038/s41576-019-0173-8
doi: 10.1038/s41576-019-0173-8
pubmed: 31605096
Andersson R, Gebhard C, Miguel-Escalada I et al (2014) An atlas of active enhancers across human cell types and tissues. Nature 507:455–461. https://doi.org/10.1038/nature12787
doi: 10.1038/nature12787
pubmed: 24670763
pmcid: 5215096
Andersson R, Sandelin A, Danko CG (2015) A unified architecture of transcriptional regulatory elements. Trends Genet 31:426–433. https://doi.org/10.1016/j.tig.2015.05.007
doi: 10.1016/j.tig.2015.05.007
pubmed: 26073855
Ardui S, Ameur A, Vermeesch JR, Hestand MS (2018) Single molecule real-time (SMRT) sequencing comes of age: applications and utilities for medical diagnostics. Nucleic Acids Res 46:2159–2168
doi: 10.1093/nar/gky066
pubmed: 29401301
pmcid: 5861413
Arnold CD, Gerlach D, Stelzer C et al (2013) Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 339:1074–1077. https://doi.org/10.1126/science.1232542
doi: 10.1126/science.1232542
pubmed: 23328393
Asthana S, Noble WS, Kryukov G et al (2007) Widely distributed noncoding purifying selection in the human genome. Proc Natl Acad Sci U S A 104:12410–12415. https://doi.org/10.1073/pnas.0705140104
doi: 10.1073/pnas.0705140104
pubmed: 17640883
pmcid: 1941483
Avsec Ž, Agarwal V, Visentin D et al (2021a) Effective gene expression prediction from sequence by integrating long-range interactions. Nat Methods 18:1196–1203. https://doi.org/10.1038/s41592-021-01252-x
doi: 10.1038/s41592-021-01252-x
pubmed: 34608324
pmcid: 8490152
Avsec Ž, Weilert M, Shrikumar A et al (2021b) Base-resolution models of transcription-factor binding reveal soft motif syntax. Nat Genet 53:354–366. https://doi.org/10.1038/s41588-021-00782-6
doi: 10.1038/s41588-021-00782-6
pubmed: 33603233
pmcid: 8812996
Bailey T, Krajewski P, Ladunga I et al (2013) Practical guidelines for the comprehensive analysis of ChIP-seq data. PLoS Comput Biol 9:e1003326. https://doi.org/10.1371/journal.pcbi.1003326
doi: 10.1371/journal.pcbi.1003326
pubmed: 24244136
pmcid: 3828144
Banerji J, Olson L, Schaffner W (1983) A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell 33:729–740. https://doi.org/10.1016/0092-8674(83)90015-6
doi: 10.1016/0092-8674(83)90015-6
pubmed: 6409418
Batut P, Dobin A, Plessy C et al (2013) High-fidelity promoter profiling reveals widespread alternative promoter usage and transposon-driven developmental gene expression. Genome Res 23:169–180. https://doi.org/10.1101/gr.139618.112
doi: 10.1101/gr.139618.112
pubmed: 22936248
pmcid: 3530677
Baylin SB, Jones PA (2016) Epigenetic determinants of cancer. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a019505
doi: 10.1101/cshperspect.a019505
pubmed: 27194046
pmcid: 5008069
Beagrie RA, Scialdone A, Schueler M et al (2017) Complex multi-enhancer contacts captured by genome architecture mapping. Nature 543:519–524. https://doi.org/10.1038/nature21411
doi: 10.1038/nature21411
pubmed: 28273065
pmcid: 5366070
Becker JS, Nicetto D, Zaret KS (2016) H3K9me3-dependent heterochromatin: barrier to cell fate changes. Trends Genet 32:29–41. https://doi.org/10.1016/j.tig.2015.11.001
doi: 10.1016/j.tig.2015.11.001
pubmed: 26675384
Becker JS, McCarthy RL, Sidoli S et al (2017) Genomic and proteomic resolution of heterochromatin and its restriction of alternate fate genes. Mol Cell 68:1023-1037.e15. https://doi.org/10.1016/j.molcel.2017.11.030
doi: 10.1016/j.molcel.2017.11.030
pubmed: 29272703
pmcid: 5858919
Bender CM, Gonzalgo ML, Gonzales FA et al (1999) Roles of cell division and gene transcription in the methylation of CpG islands. Mol Cell Biol 19:6690–6698. https://doi.org/10.1128/MCB.19.10.6690
doi: 10.1128/MCB.19.10.6690
pubmed: 10490608
pmcid: 84656
Bernstein BE, Mikkelsen TS, Xie X et al (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315–326. https://doi.org/10.1016/j.cell.2006.02.041
doi: 10.1016/j.cell.2006.02.041
pubmed: 16630819
Bird AP, Taggart MH (1980) Variable patterns of total DNA and rDNA methylation in animals. Nucleic Acids Res 8:1485–1497. https://doi.org/10.1093/nar/8.7.1485
doi: 10.1093/nar/8.7.1485
pubmed: 6253937
pmcid: 324011
Bird A, Taggart M, Frommer M et al (1985) A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell 40:91–99. https://doi.org/10.1016/0092-8674(85)90312-5
doi: 10.1016/0092-8674(85)90312-5
pubmed: 2981636
Blackwood EM, Kadonaga JT (1998) Going the distance: a current view of enhancer action. Science 281:60–63. https://doi.org/10.1126/science.281.5373.60
doi: 10.1126/science.281.5373.60
pubmed: 9679020
Boix CA, James BT, Park YP et al (2021) Regulatory genomic circuitry of human disease loci by integrative epigenomics. Nature 590:300–307. https://doi.org/10.1038/s41586-020-03145-z
doi: 10.1038/s41586-020-03145-z
pubmed: 33536621
pmcid: 7875769
Boyle AP, Davis S, Shulha HP et al (2008) High-resolution mapping and characterization of open chromatin across the genome. Cell 132:311–322. https://doi.org/10.1016/j.cell.2007.12.014
doi: 10.1016/j.cell.2007.12.014
pubmed: 18243105
pmcid: 2669738
Buenrostro JD, Giresi PG, Zaba LC et al (2013) Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods 10:1213–1218. https://doi.org/10.1038/nmeth.2688
doi: 10.1038/nmeth.2688
pubmed: 24097267
pmcid: 3959825
Buenrostro JD, Wu B, Litzenburger UM et al (2015) Single-cell chromatin accessibility reveals principles of regulatory variation. Nature 523:486–490. https://doi.org/10.1038/nature14590
doi: 10.1038/nature14590
pubmed: 26083756
pmcid: 4685948
Burley SK, Roeder RG (1996) Biochemistry and structural biology of transcription factor IID (TFIID). Annu Rev Biochem 65:769–799. https://doi.org/10.1146/annurev.bi.65.070196.004005
doi: 10.1146/annurev.bi.65.070196.004005
pubmed: 8811195
Cai Y, Zhang Y, Loh YP et al (2021) H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions. Nat Commun 12:719. https://doi.org/10.1038/s41467-021-20940-y
doi: 10.1038/s41467-021-20940-y
pubmed: 33514712
pmcid: 7846766
Carelli FN, Liechti A, Halbert J et al (2018) Repurposing of promoters and enhancers during mammalian evolution. Nat Commun 9:4066. https://doi.org/10.1038/s41467-018-06544-z
doi: 10.1038/s41467-018-06544-z
pubmed: 30287902
pmcid: 6172195
Carleton JB, Berrett KC, Gertz J (2017) Multiplex enhancer interference reveals collaborative control of gene regulation by estrogen receptor α-bound enhancers. Cell Syst 5:333-344.e5
doi: 10.1016/j.cels.2017.08.011
pubmed: 28964699
pmcid: 5679353
Carninci P, Sandelin A, Lenhard B et al (2006) Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38:626–635. https://doi.org/10.1038/ng1789
doi: 10.1038/ng1789
pubmed: 16645617
Chan RCW, Libbrecht MW, Roberts EG et al (2018) Segway 2.0: Gaussian mixture models and minibatch training. Bioinformatics 34:669–671. https://doi.org/10.1093/bioinformatics/btx603
doi: 10.1093/bioinformatics/btx603
pubmed: 29028889
Chandra V, Bhattacharyya S, Schmiedel BJ et al (2021) Promoter-interacting expression quantitative trait loci are enriched for functional genetic variants. Nat Genet 53:110–119. https://doi.org/10.1038/s41588-020-00745-3
doi: 10.1038/s41588-020-00745-3
pubmed: 33349701
Chatterjee S, Ahituv N (2017) Gene regulatory elements, major drivers of human disease. Annu Rev Genomics Hum Genet 18:45–63. https://doi.org/10.1146/annurev-genom-091416-035537
doi: 10.1146/annurev-genom-091416-035537
pubmed: 28399667
Cheng Y, Wu W, Kumar SA et al (2009) Erythroid GATA1 function revealed by genome-wide analysis of transcription factor occupancy, histone modifications, and mRNA expression. Genome Res 19:2172–2184. https://doi.org/10.1101/gr.098921.109
doi: 10.1101/gr.098921.109
pubmed: 19887574
pmcid: 2792182
Chiaromonte F, Weber RJ, Roskin KM et al (2003) The share of human genomic DNA under selection estimated from human-mouse genomic alignments. Cold Spring Harb Symp Quant Biol 68:245–254. https://doi.org/10.1101/sqb.2003.68.245
doi: 10.1101/sqb.2003.68.245
pubmed: 15338624
Chong JA, Tapia-Ramírez J, Kim S et al (1995) REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 80:949–957. https://doi.org/10.1016/0092-8674(95)90298-8
doi: 10.1016/0092-8674(95)90298-8
pubmed: 7697725
Cooper DN, Krawczak M (1989) Cytosine methylation and the fate of CpG dinucleotides in vertebrate genomes. Hum Genet 83:181–188. https://doi.org/10.1007/BF00286715
doi: 10.1007/BF00286715
pubmed: 2777259
Cooper GM, Stone EA, Asimenos G et al (2005) Distribution and intensity of constraint in mammalian genomic sequence. Genome Res 15:901–913. https://doi.org/10.1101/gr.3577405
doi: 10.1101/gr.3577405
pubmed: 15965027
pmcid: 1172034
Corces MR, Trevino AE, Hamilton EG et al (2017) An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat Methods 14:959–962. https://doi.org/10.1038/nmeth.4396
doi: 10.1038/nmeth.4396
pubmed: 28846090
pmcid: 5623106
Core LJ, Waterfall JJ, Lis JT (2008) Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322:1845–1848. https://doi.org/10.1126/science.1162228
doi: 10.1126/science.1162228
pubmed: 19056941
pmcid: 2833333
Core LJ, Martins AL, Danko CG et al (2014) Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers. Nat Genet 46:1311–1320. https://doi.org/10.1038/ng.3142
doi: 10.1038/ng.3142
pubmed: 25383968
pmcid: 4254663
Creyghton MP, Cheng AW, Welstead GG et al (2010) Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A 107:21931–21936. https://doi.org/10.1073/pnas.1016071107
doi: 10.1073/pnas.1016071107
pubmed: 21106759
pmcid: 3003124
Dao LTM, Galindo-Albarrán AO, Castro-Mondragon JA et al (2017) Genome-wide characterization of mammalian promoters with distal enhancer functions. Nat Genet 49:1073–1081. https://doi.org/10.1038/ng.3884
doi: 10.1038/ng.3884
pubmed: 28581502
Davies JOJ, Oudelaar AM, Higgs DR, Hughes JR (2017) How best to identify chromosomal interactions: a comparison of approaches. Nat Methods 14:125–134. https://doi.org/10.1038/nmeth.4146
doi: 10.1038/nmeth.4146
pubmed: 28139673
de Almeida BP, Reiter F, Pagani M, Stark A (2022) DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers. Nat Genet 54:613–624. https://doi.org/10.1038/s41588-022-01048-5
doi: 10.1038/s41588-022-01048-5
pubmed: 35551305
De Santa F, Barozzi I, Mietton F et al (2010) A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol 8:e1000384. https://doi.org/10.1371/journal.pbio.1000384
doi: 10.1371/journal.pbio.1000384
pubmed: 20485488
pmcid: 2867938
Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. Genes Dev 25:1010–1022. https://doi.org/10.1101/gad.2037511
doi: 10.1101/gad.2037511
pubmed: 21576262
pmcid: 3093116
Dekker J, Rippe K, Dekker M, Kleckner N (2002) Capturing chromosome conformation. Science 295:1306–1311. https://doi.org/10.1126/science.1067799
doi: 10.1126/science.1067799
pubmed: 11847345
Diao Y, Fang R, Li B et al (2017) A tiling-deletion-based genetic screen for cis-regulatory element identification in mammalian cells. Nat Methods 14:629–635
doi: 10.1038/nmeth.4264
pubmed: 28417999
pmcid: 5490986
Dixit A, Parnas O, Li B et al (2016) Perturb-Seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens. Cell 167:1853-1866.e17. https://doi.org/10.1016/j.cell.2016.11.038
doi: 10.1016/j.cell.2016.11.038
pubmed: 27984732
pmcid: 5181115
Doni Jayavelu N, Jajodia A, Mishra A, Hawkins RD (2020) Candidate silencer elements for the human and mouse genomes. Nat Commun 11:1061. https://doi.org/10.1038/s41467-020-14853-5
doi: 10.1038/s41467-020-14853-5
pubmed: 32103011
pmcid: 7044160
Dostie J, Richmond TA, Arnaout RA et al (2006) Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res 16:1299–1309. https://doi.org/10.1101/gr.5571506
doi: 10.1101/gr.5571506
pubmed: 16954542
pmcid: 1581439
Driscoll MC, Dobkin CS, Alter BP (1989) Gamma delta beta-thalassemia due to a de novo mutation deleting the 5’ beta-globin gene activation-region hypersensitive sites. Proc Natl Acad Sci U S A 86:7470–7474. https://doi.org/10.1073/pnas.86.19.7470
doi: 10.1073/pnas.86.19.7470
pubmed: 2798417
pmcid: 298086
Ehret CF, de Haller G (1963) Origin, development and maturation of organelles and organelle systems of the cell surface in paramecium. J Ultrastruct Res 23(SUPPL6):1–42. https://doi.org/10.1016/s0022-5320(63)80088-x
doi: 10.1016/s0022-5320(63)80088-x
Elliott K, Larsson E (2021) Non-coding driver mutations in human cancer. Nat Rev Cancer 21:500–509. https://doi.org/10.1038/s41568-021-00371-z
doi: 10.1038/s41568-021-00371-z
pubmed: 34230647
Emorine L, Kuehl M, Weir L et al (1983) A conserved sequence in the immunoglobulin Jκ–Cκ intron: possible enhancer element. Nature 304:447–449. https://doi.org/10.1038/304447a0
doi: 10.1038/304447a0
pubmed: 6308460
ENCODE Project Consortium (2004) The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306:636–640. https://doi.org/10.1126/science.1105136
doi: 10.1126/science.1105136
ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74. https://doi.org/10.1038/nature11247
doi: 10.1038/nature11247
ENCODE Project Consortium, Moore JE, Purcaro MJ et al (2020) Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583:699–710. https://doi.org/10.1038/s41586-020-2493-4
doi: 10.1038/s41586-020-2493-4
Epstein DJ (2009) Cis-regulatory mutations in human disease. Brief Funct Genom Proteom 8:310–316. https://doi.org/10.1093/bfgp/elp021
doi: 10.1093/bfgp/elp021
Ernst J, Kellis M (2010) Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat Biotechnol 28:817–825. https://doi.org/10.1038/nbt.1662
doi: 10.1038/nbt.1662
pubmed: 20657582
pmcid: 2919626
Ernst J, Kellis M (2012) ChromHMM: automating chromatin-state discovery and characterization. Nat Methods 9:215–216. https://doi.org/10.1038/nmeth.1906
doi: 10.1038/nmeth.1906
pubmed: 22373907
pmcid: 3577932
Ernst J, Kellis M (2017) Chromatin-state discovery and genome annotation with ChromHMM. Nat Protoc 12:2478–2492. https://doi.org/10.1038/nprot.2017.124
doi: 10.1038/nprot.2017.124
pubmed: 29120462
pmcid: 5945550
Fan K, Moore JE, Zhang X-O, Weng Z (2021) Genetic and epigenetic features of promoters with ubiquitous chromatin accessibility support ubiquitous transcription of cell-essential genes. Nucleic Acids Res 49:5705–5725. https://doi.org/10.1093/nar/gkab345
doi: 10.1093/nar/gkab345
pubmed: 33978759
pmcid: 8191798
Feng S, Cokus SJ, Zhang X et al (2010) Conservation and divergence of methylation patterning in plants and animals. Proc Natl Acad Sci USA 107:8689–8694. https://doi.org/10.1073/pnas.1002720107
doi: 10.1073/pnas.1002720107
pubmed: 20395551
pmcid: 2889301
Frankish A, Diekhans M, Ferreira A-M et al (2019) GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res 47:D766–D773. https://doi.org/10.1093/nar/gky955
doi: 10.1093/nar/gky955
pubmed: 30357393
Frankish A, Diekhans M, Jungreis I et al (2021) GENCODE 2021. Nucleic Acids Res 49:D916–D923. https://doi.org/10.1093/nar/gkaa1087
doi: 10.1093/nar/gkaa1087
pubmed: 33270111
Frazer KA, Tao H, Osoegawa K et al (2004) Noncoding sequences conserved in a limited number of mammals in the SIM2 interval are frequently functional. Genome Res 14:367–372. https://doi.org/10.1101/gr.1961204
doi: 10.1101/gr.1961204
pubmed: 14962988
pmcid: 353216
French JD, Edwards SL (2020) The role of noncoding variants in heritable disease. Trends Genet 36:880–891. https://doi.org/10.1016/j.tig.2020.07.004
doi: 10.1016/j.tig.2020.07.004
pubmed: 32741549
Fu S, Wang Q, Moore JE et al (2018) Differential analysis of chromatin accessibility and histone modifications for predicting mouse developmental enhancers. Nucleic Acids Res 46:11184–11201. https://doi.org/10.1093/nar/gky753
doi: 10.1093/nar/gky753
pubmed: 30137428
pmcid: 6265487
Fuke C, Shimabukuro M, Petronis A et al (2004) Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet 68:196–204. https://doi.org/10.1046/j.1529-8817.2004.00081.x
doi: 10.1046/j.1529-8817.2004.00081.x
pubmed: 15180700
Gardiner-Garden M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196:261–282. https://doi.org/10.1016/0022-2836(87)90689-9
doi: 10.1016/0022-2836(87)90689-9
pubmed: 3656447
Gershenzon NI, Ioshikhes IP (2005) Synergy of human Pol II core promoter elements revealed by statistical sequence analysis. Bioinformatics 21:1295–1300. https://doi.org/10.1093/bioinformatics/bti172
doi: 10.1093/bioinformatics/bti172
pubmed: 15572469
Gillies SD, Morrison SL, Oi VT, Tonegawa S (1983) A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell 33:717–728. https://doi.org/10.1016/0092-8674(83)90014-4
doi: 10.1016/0092-8674(83)90014-4
pubmed: 6409417
Greenberg MVC, Bourc’his D (2019) The diverse roles of DNA methylation in mammalian development and disease. Nat Rev Mol Cell Biol 20:590–607. https://doi.org/10.1038/s41580-019-0159-6
doi: 10.1038/s41580-019-0159-6
pubmed: 31399642
Greener JG, Kandathil SM, Moffat L, Jones DT (2022) A guide to machine learning for biologists. Nat Rev Mol Cell Biol 23:40–55. https://doi.org/10.1038/s41580-021-00407-0
doi: 10.1038/s41580-021-00407-0
pubmed: 34518686
Grice EA, Rochelle ES, Green ED et al (2005) Evaluation of the RET regulatory landscape reveals the biological relevance of a HSCR-implicated enhancer. Hum Mol Genet 14:3837–3845. https://doi.org/10.1093/hmg/ddi408
doi: 10.1093/hmg/ddi408
pubmed: 16269442
GTEx Consortium (2020) The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369:1318–1330. https://doi.org/10.1126/science.aaz1776
doi: 10.1126/science.aaz1776
Haberle V, Stark A (2018) Eukaryotic core promoters and the functional basis of transcription initiation. Nat Rev Mol Cell Biol 19:621–637. https://doi.org/10.1038/s41580-018-0028-8
doi: 10.1038/s41580-018-0028-8
pubmed: 29946135
pmcid: 6205604
Haberle V, Arnold CD, Pagani M et al (2019) Transcriptional cofactors display specificity for distinct types of core promoters. Nature 570:122–126. https://doi.org/10.1038/s41586-019-1210-7
doi: 10.1038/s41586-019-1210-7
pubmed: 31092928
pmcid: 7613045
Hager GL, Sabo P, Thurman R et al (2009) Interaction of the glucocorticoid receptor with the chromatin landscape. FASEB J 23:487.3. https://doi.org/10.1096/fasebj.23.1_supplement.487.3
doi: 10.1096/fasebj.23.1_supplement.487.3
Hah N, Murakami S, Nagari A et al (2013) Enhancer transcripts mark active estrogen receptor binding sites. Genome Res 23:1210–1223. https://doi.org/10.1101/gr.152306.112
doi: 10.1101/gr.152306.112
pubmed: 23636943
pmcid: 3730096
Hansen TJ, Hodges E (2022) ATAC-STARR-seq reveals transcription factor-bound activators and silencers across the chromatin accessible human genome. Genome Res. https://doi.org/10.1101/gr.276766.122
doi: 10.1101/gr.276766.122
pubmed: 35858748
pmcid: 9435738
Hardison RC (2012) Genome-wide epigenetic data facilitate understanding of disease susceptibility association studies. J Biol Chem 287:30932–30940. https://doi.org/10.1074/jbc.R112.352427
doi: 10.1074/jbc.R112.352427
pubmed: 22952232
pmcid: 3438926
Harrow J, Frankish A, Gonzalez JM et al (2012) GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res 22:1760–1774. https://doi.org/10.1101/gr.135350.111
doi: 10.1101/gr.135350.111
pubmed: 22955987
pmcid: 3431492
He HH, Meyer CA, Hu SS et al (2014) Refined DNase-seq protocol and data analysis reveals intrinsic bias in transcription factor footprint identification. Nat Methods 11:73–78. https://doi.org/10.1038/nmeth.2762
doi: 10.1038/nmeth.2762
pubmed: 24317252
He Y, Hariharan M, Gorkin DU et al (2020) Spatiotemporal DNA methylome dynamics of the developing mouse fetus. Nature 583:752–759. https://doi.org/10.1038/s41586-020-2119-x
doi: 10.1038/s41586-020-2119-x
pubmed: 32728242
pmcid: 7398276
Heintzman ND, Stuart RK, Hon G et al (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39:311–318. https://doi.org/10.1038/ng1966
doi: 10.1038/ng1966
pubmed: 17277777
Herz H-M, Hu D, Shilatifard A (2014) Enhancer malfunction in cancer. Mol Cell 53:859–866. https://doi.org/10.1016/j.molcel.2014.02.033
doi: 10.1016/j.molcel.2014.02.033
pubmed: 24656127
pmcid: 4049186
Hesselberth JR, Chen X, Zhang Z et al (2009) Global mapping of protein-DNA interactions in vivo by digital genomic footprinting. Nat Methods 6:283–289. https://doi.org/10.1038/nmeth.1313
doi: 10.1038/nmeth.1313
pubmed: 19305407
pmcid: 2668528
Hindorff LA, Sethupathy P, Junkins HA et al (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 106:9362–9367. https://doi.org/10.1073/pnas.0903103106
doi: 10.1073/pnas.0903103106
pubmed: 19474294
pmcid: 2687147
Hirabayashi S, Bhagat S, Matsuki Y et al (2019) NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements. Nat Genet 51:1369–1379. https://doi.org/10.1038/s41588-019-0485-9
doi: 10.1038/s41588-019-0485-9
pubmed: 31477927
Hoffman MM, Buske OJ, Wang J et al (2012) Unsupervised pattern discovery in human chromatin structure through genomic segmentation. Nat Methods 9:473–476. https://doi.org/10.1038/nmeth.1937
doi: 10.1038/nmeth.1937
pubmed: 22426492
pmcid: 3340533
Holliday R, Grigg GW (1993) DNA methylation and mutation. Mutat Res 285:61–67. https://doi.org/10.1016/0027-5107(93)90052-h
doi: 10.1016/0027-5107(93)90052-h
pubmed: 7678134
Holtzman L, Gersbach CA (2018) Editing the epigenome: reshaping the genomic landscape. Annu Rev Genomics Hum Genet 19:43–71. https://doi.org/10.1146/annurev-genom-083117-021632
doi: 10.1146/annurev-genom-083117-021632
pubmed: 29852072
Hon GC, Hawkins RD, Caballero OL et al (2012) Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer. Genome Res 22:246–258. https://doi.org/10.1101/gr.125872.111
doi: 10.1101/gr.125872.111
pubmed: 22156296
pmcid: 3266032
Hsieh C-L, Fei T, Chen Y et al (2014) Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation. Proc Natl Acad Sci USA 111:7319–7324. https://doi.org/10.1073/pnas.1324151111
doi: 10.1073/pnas.1324151111
pubmed: 24778216
pmcid: 4034202
Hsieh T-HS, Weiner A, Lajoie B et al (2015) Mapping nucleosome resolution chromosome folding in yeast by micro-C. Cell 162:108–119. https://doi.org/10.1016/j.cell.2015.05.048
doi: 10.1016/j.cell.2015.05.048
pubmed: 26119342
pmcid: 4509605
Hsieh T-HS, Cattoglio C, Slobodyanyuk E et al (2020) Resolving the 3D landscape of transcription-linked mammalian chromatin folding. Mol Cell 78:539-553.e8. https://doi.org/10.1016/j.molcel.2020.03.002
doi: 10.1016/j.molcel.2020.03.002
pubmed: 32213323
pmcid: 7703524
Hsu PD, Lander ES, Zhang F (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157:1262–1278. https://doi.org/10.1016/j.cell.2014.05.010
doi: 10.1016/j.cell.2014.05.010
pubmed: 24906146
pmcid: 4343198
Huang D, Ovcharenko I (2022) Enhancer–silencer transitions in the human genome. Genome Res 32:437–448. https://doi.org/10.1101/gr.275992.121
doi: 10.1101/gr.275992.121
pubmed: 35105669
pmcid: 8896465
Huang D, Petrykowska HM, Miller BF et al (2019) Identification of human silencers by correlating cross-tissue epigenetic profiles and gene expression. Genome Res 29:657–667. https://doi.org/10.1101/gr.247007.118
doi: 10.1101/gr.247007.118
pubmed: 30886051
pmcid: 6442386
International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431:931–945. https://doi.org/10.1038/nature03001
doi: 10.1038/nature03001
Jeon H, Lee H, Kang B et al (2020) Comparative analysis of commonly used peak calling programs for ChIP-Seq analysis. Genom Inform 18:e42. https://doi.org/10.5808/GI.2020.18.4.e42
doi: 10.5808/GI.2020.18.4.e42
Jin Y, Eser U, Struhl K, Churchman LS (2017) The ground state and evolution of promoter region directionality. Cell 170:889-898.e10. https://doi.org/10.1016/j.cell.2017.07.006
doi: 10.1016/j.cell.2017.07.006
pubmed: 28803729
pmcid: 5576552
Jing H, Vakoc CR, Ying L et al (2008) Exchange of GATA factors mediates transitions in looped chromatin organization at a developmentally regulated gene locus. Mol Cell 29:232–242. https://doi.org/10.1016/j.molcel.2007.11.020
doi: 10.1016/j.molcel.2007.11.020
pubmed: 18243117
pmcid: 2254447
Johnson DS, Davidson B, Brown CD et al (2004) Noncoding regulatory sequences of Ciona exhibit strong correspondence between evolutionary constraint and functional importance. Genome Res 14:2448–2456. https://doi.org/10.1101/gr.2964504
doi: 10.1101/gr.2964504
pubmed: 15545496
pmcid: 534669
Johnson DS, Mortazavi A, Myers RM, Wold B (2007) Genome-wide mapping of in vivo protein-DNA interactions. Science 316:1497–1502. https://doi.org/10.1126/science.1141319
doi: 10.1126/science.1141319
pubmed: 17540862
Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13:484–492. https://doi.org/10.1038/nrg3230
doi: 10.1038/nrg3230
pubmed: 22641018
Kadonaga JT (2012) Perspectives on the RNA polymerase II core promoter. Wiley Interdiscip Rev Dev Biol 1:40–51. https://doi.org/10.1002/wdev.21
doi: 10.1002/wdev.21
pubmed: 23801666
Kelley DR, Snoek J, Rinn JL (2016) Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks. Genome Res 26:990–999. https://doi.org/10.1101/gr.200535.115
doi: 10.1101/gr.200535.115
pubmed: 27197224
pmcid: 4937568
Kelley DR, Reshef YA, Bileschi M et al (2018) Sequential regulatory activity prediction across chromosomes with convolutional neural networks. Genome Res 28:739–750. https://doi.org/10.1101/gr.227819.117
doi: 10.1101/gr.227819.117
pubmed: 29588361
pmcid: 5932613
Kellis M, Wold B, Snyder MP et al (2014) Defining functional DNA elements in the human genome. Proc Natl Acad Sci U S A 111:6131–6138. https://doi.org/10.1073/pnas.1318948111
doi: 10.1073/pnas.1318948111
pubmed: 24753594
pmcid: 4035993
Kichaev G, Pasaniuc B (2015) Leveraging functional-annotation data in trans-ethnic fine-mapping studies. Am J Hum Genet 97:260–271. https://doi.org/10.1016/j.ajhg.2015.06.007
doi: 10.1016/j.ajhg.2015.06.007
pubmed: 26189819
pmcid: 4573268
Kichaev G, Yang W-Y, Lindstrom S et al (2014) Integrating functional data to prioritize causal variants in statistical fine-mapping studies. PLoS Genet 10:e1004722. https://doi.org/10.1371/journal.pgen.1004722
doi: 10.1371/journal.pgen.1004722
pubmed: 25357204
pmcid: 4214605
Kim T-K, Hemberg M, Gray JM et al (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465:182–187. https://doi.org/10.1038/nature09033
doi: 10.1038/nature09033
pubmed: 20393465
pmcid: 3020079
Kim S, Yu N-K, Kaang B-K (2015) CTCF as a multifunctional protein in genome regulation and gene expression. Exp Mol Med 47:e166. https://doi.org/10.1038/emm.2015.33
doi: 10.1038/emm.2015.33
pubmed: 26045254
pmcid: 4491725
Kioussis D, Vanin E, deLange T et al (1983) β-Globin gene inactivation by DNA translocation in γβ-thalassemia. Nature 306:662–666. https://doi.org/10.1038/306662a0
doi: 10.1038/306662a0
pubmed: 6318113
Kleinjan DJ, van Heyningen V (1998) Position effect in human genetic disease. Hum Mol Genet 7:1611–1618. https://doi.org/10.1093/hmg/7.10.1611
doi: 10.1093/hmg/7.10.1611
pubmed: 9735382
Klemm SL, Shipony Z, Greenleaf WJ (2019) Chromatin accessibility and the regulatory epigenome. Nat Rev Genet 20:207–220. https://doi.org/10.1038/s41576-018-0089-8
doi: 10.1038/s41576-018-0089-8
pubmed: 30675018
Koido M, Hon C-C, Koyama S et al (2022) Prediction of the cell-type-specific transcription of non-coding RNAs from genome sequences via machine learning. Nat Biomed Eng. https://doi.org/10.1038/s41551-022-00961-8
doi: 10.1038/s41551-022-00961-8
pubmed: 36411359
Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705. https://doi.org/10.1016/j.cell.2007.02.005
doi: 10.1016/j.cell.2007.02.005
pubmed: 17320507
Krietenstein N, Abraham S, Venev SV et al (2020) Ultrastructural details of mammalian chromosome architecture. Mol Cell 78:554-565.e7. https://doi.org/10.1016/j.molcel.2020.03.003
doi: 10.1016/j.molcel.2020.03.003
pubmed: 32213324
pmcid: 7222625
Kruesi WS, Core LJ, Waters CT et al (2013) Condensin controls recruitment of RNA polymerase II to achieve nematode X-chromosome dosage compensation. Elife 2:e00808. https://doi.org/10.7554/eLife.00808
doi: 10.7554/eLife.00808
pubmed: 23795297
pmcid: 3687364
Kwak H, Fuda NJ, Core LJ, Lis JT (2013) Precise maps of RNA polymerase reveal how promoters direct initiation and pausing. Science 339:950–953. https://doi.org/10.1126/science.1229386
doi: 10.1126/science.1229386
pubmed: 23430654
pmcid: 3974810
Lambert SA, Jolma A, Campitelli LF et al (2018) The human transcription factors. Cell 172:650–665. https://doi.org/10.1016/j.cell.2018.01.029
doi: 10.1016/j.cell.2018.01.029
pubmed: 29425488
Larsen F, Gundersen G, Lopez R, Prydz H (1992) CpG islands as gene markers in the human genome. Genomics 13:1095–1107. https://doi.org/10.1016/0888-7543(92)90024-m
doi: 10.1016/0888-7543(92)90024-m
pubmed: 1505946
Laurent L, Wong E, Li G et al (2010) Dynamic changes in the human methylome during differentiation. Genome Res 20:320–331. https://doi.org/10.1101/gr.101907.109
doi: 10.1101/gr.101907.109
pubmed: 20133333
pmcid: 2840979
LeCun Y, Boser B, Denker JS et al (1989) Backpropagation applied to handwritten zip code recognition. Neural Comput 1:541–551. https://doi.org/10.1162/neco.1989.1.4.541
doi: 10.1162/neco.1989.1.4.541
Lesurf R, Cotto KC, Wang G et al (2015) ORegAnno 3.0: a community-driven resource for curated regulatory annotation. Nucleic Acids Res 44:D126–D132. https://doi.org/10.1093/nar/gkv1203
doi: 10.1093/nar/gkv1203
pubmed: 26578589
pmcid: 4702855
Lettice LA, Heaney SJH, Purdie LA et al (2003) A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet 12:1725–1735. https://doi.org/10.1093/hmg/ddg180
doi: 10.1093/hmg/ddg180
pubmed: 12837695
Lev Maor G, Yearim A, Ast G (2015) The alternative role of DNA methylation in splicing regulation. Trends Genet 31:274–280. https://doi.org/10.1016/j.tig.2015.03.002
doi: 10.1016/j.tig.2015.03.002
pubmed: 25837375
Leviyang S (2021) Interferon stimulated binding of ISRE is cell type specific and is predicted by homeostatic chromatin state. Cytokine X 3:100056. https://doi.org/10.1016/j.cytox.2021.100056
doi: 10.1016/j.cytox.2021.100056
pubmed: 34409284
pmcid: 8361084
Li E, Zhang Y (2014) DNA methylation in mammals. Cold Spring Harb Perspect Biol 6:a019133. https://doi.org/10.1101/cshperspect.a019133
doi: 10.1101/cshperspect.a019133
pubmed: 24789823
pmcid: 3996472
Li G, Ruan X, Auerbach RK et al (2012) Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 148:84–98. https://doi.org/10.1016/j.cell.2011.12.014
doi: 10.1016/j.cell.2011.12.014
pubmed: 22265404
pmcid: 3339270
Li W, Notani D, Ma Q et al (2013) Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498:516–520. https://doi.org/10.1038/nature12210
doi: 10.1038/nature12210
pubmed: 23728302
pmcid: 3718886
Li Y, Zheng H, Wang Q et al (2018) Genome-wide analyses reveal a role of Polycomb in promoting hypomethylation of DNA methylation valleys. Genome Biol 19:18. https://doi.org/10.1186/s13059-018-1390-8
doi: 10.1186/s13059-018-1390-8
pubmed: 29422066
pmcid: 5806489
Liang D, Elwell AL, Aygün N et al (2021) Cell-type-specific effects of genetic variation on chromatin accessibility during human neuronal differentiation. Nat Neurosci 24:941–953. https://doi.org/10.1038/s41593-021-00858-w
doi: 10.1038/s41593-021-00858-w
pubmed: 34017130
pmcid: 8254789
Libbrecht MW, Rodriguez OL, Weng Z et al (2019) A unified encyclopedia of human functional DNA elements through fully automated annotation of 164 human cell types. Genome Biol 20:180. https://doi.org/10.1186/s13059-019-1784-2
doi: 10.1186/s13059-019-1784-2
pubmed: 31462275
pmcid: 6714098
Lieberman-Aiden E, van Berkum NL, Williams L et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–293. https://doi.org/10.1126/science.1181369
doi: 10.1126/science.1181369
pubmed: 19815776
pmcid: 2858594
Lim CY, Santoso B, Boulay T et al (2004) The MTE, a new core promoter element for transcription by RNA polymerase II. Genes Dev 18:1606–1617. https://doi.org/10.1101/gad.1193404
doi: 10.1101/gad.1193404
pubmed: 15231738
pmcid: 443522
Lindblad-Toh K, Garber M, Zuk O et al (2011) A high-resolution map of human evolutionary constraint using 29 mammals. Nature 478:476–482. https://doi.org/10.1038/nature10530
doi: 10.1038/nature10530
pubmed: 21993624
pmcid: 3207357
Linzer N, Trumbull A, Nar R et al (2021) Regulation of RNA polymerase II transcription initiation and elongation by transcription factor TFII-I. Front Mol Biosci 8:681550. https://doi.org/10.3389/fmolb.2021.681550
doi: 10.3389/fmolb.2021.681550
pubmed: 34055891
pmcid: 8155576
Lister R, Pelizzola M, Dowen RH et al (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315–322. https://doi.org/10.1038/nature08514
doi: 10.1038/nature08514
pubmed: 19829295
pmcid: 2857523
Logsdon GA, Vollger MR, Eichler EE (2020) Long-read human genome sequencing and its applications. Nat Rev Genet 21:597–614. https://doi.org/10.1038/s41576-020-0236-x
doi: 10.1038/s41576-020-0236-x
pubmed: 32504078
pmcid: 7877196
Loots GG, Locksley RM, Blankespoor CM et al (2000) Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 288:136–140. https://doi.org/10.1126/science.288.5463.136
doi: 10.1126/science.288.5463.136
pubmed: 10753117
Louder RK, He Y, López-Blanco JR et al (2016) Corrigendum: structure of promoter-bound TFIID and model of human pre-initiation complex assembly. Nature 536:112. https://doi.org/10.1038/nature17984
doi: 10.1038/nature17984
pubmed: 27096372
Magnuson B, Veloso A, Kirkconnell KS et al (2015) Identifying transcription start sites and active enhancer elements using BruUV-seq. Sci Rep 5:17978. https://doi.org/10.1038/srep17978
doi: 10.1038/srep17978
pubmed: 26656874
pmcid: 4675984
Manolio TA, Collins FS, Cox NJ et al (2009) Finding the missing heritability of complex diseases. Nature 461:747–753. https://doi.org/10.1038/nature08494
doi: 10.1038/nature08494
pubmed: 19812666
pmcid: 2831613
Marasca F, Bodega B, Orlando V (2018) How polycomb-mediated cell memory deals with a changing environment. BioEssays 40:1700137
doi: 10.1002/bies.201700137
Marco E, Meuleman W, Huang J et al (2017) Multi-scale chromatin state annotation using a hierarchical hidden Markov model. Nat Commun 8:15011. https://doi.org/10.1038/ncomms15011
doi: 10.1038/ncomms15011
pubmed: 28387224
pmcid: 5385569
Martowicz ML, Grass JA, Boyer ME et al (2005) Dynamic GATA factor interplay at a multicomponent regulatory region of the GATA-2 locus. J Biol Chem 280:1724–1732. https://doi.org/10.1074/jbc.M406038200
doi: 10.1074/jbc.M406038200
pubmed: 15494394
Maston GA, Evans SK, Green MR (2006) Transcriptional regulatory elements in the human genome. Annu Rev Genom Hum Genet 7:29–59. https://doi.org/10.1146/annurev.genom.7.080505.115623
doi: 10.1146/annurev.genom.7.080505.115623
Maunakea AK, Nagarajan RP, Bilenky M et al (2010) Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 466:253–257. https://doi.org/10.1038/nature09165
doi: 10.1038/nature09165
pubmed: 20613842
pmcid: 3998662
Maunakea AK, Chepelev I, Cui K, Zhao K (2013) Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. Cell Res 23:1256–1269. https://doi.org/10.1038/cr.2013.110
doi: 10.1038/cr.2013.110
pubmed: 23938295
pmcid: 3817542
Maurano MT, Humbert R, Rynes E et al (2012) Systematic localization of common disease-associated variation in regulatory DNA. Science 337:1190–1195
doi: 10.1126/science.1222794
pubmed: 22955828
pmcid: 3771521
Mayer A, di Iulio J, Maleri S et al (2015) Native elongating transcript sequencing reveals human transcriptional activity at nucleotide resolution. Cell 161:541–554. https://doi.org/10.1016/j.cell.2015.03.010
doi: 10.1016/j.cell.2015.03.010
pubmed: 25910208
pmcid: 4528962
Mayran A, Drouin J (2018) Pioneer transcription factors shape the epigenetic landscape. J Biol Chem 293:13795–13804. https://doi.org/10.1074/jbc.R117.001232
doi: 10.1074/jbc.R117.001232
pubmed: 29507097
pmcid: 6130937
Melnikov A, Murugan A, Zhang X et al (2012) Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay. Nat Biotechnol 30:271–277. https://doi.org/10.1038/nbt.2137
doi: 10.1038/nbt.2137
pubmed: 22371084
pmcid: 3297981
Mercola M, Wang XF, Olsen J, Calame K (1983) Transcriptional enhancer elements in the mouse immunoglobulin heavy chain locus. Science 221:663–665. https://doi.org/10.1126/science.6306772
doi: 10.1126/science.6306772
pubmed: 6306772
Merkenschlager M, Nora EP (2016) CTCF and cohesin in genome folding and transcriptional gene regulation. Annu Rev Genom Hum Genet 17:17–43. https://doi.org/10.1146/annurev-genom-083115-022339
doi: 10.1146/annurev-genom-083115-022339
Mifsud B, Tavares-Cadete F, Young AN et al (2015) Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nat Genet 47:598–606. https://doi.org/10.1038/ng.3286
doi: 10.1038/ng.3286
pubmed: 25938943
Miraldi ER, Chen X, Weirauch MT (2021) Deciphering cis-regulatory grammar with deep learning. Nat Genet 53:266–268
doi: 10.1038/s41588-021-00814-1
pubmed: 33686263
Mitsis T, Efthimiadou A, Bacopoulou F et al (2020) Transcription factors and evolution: an integral part of gene expression (Review). World Acad Sci J. https://doi.org/10.3892/wasj.2020.32
doi: 10.3892/wasj.2020.32
Molina N, Suter DM, Cannavo R et al (2013) Stimulus-induced modulation of transcriptional bursting in a single mammalian gene. Proc Natl Acad Sci U S A 110:20563–20568. https://doi.org/10.1073/pnas.1312310110
doi: 10.1073/pnas.1312310110
pubmed: 24297917
pmcid: 3870742
Moore JE, Zhang X-O, Elhajjajy SI et al (2022) Integration of high-resolution promoter profiling assays reveals novel, cell type-specific transcription start sites across 115 human cell and tissue types. Genome Res 32:389–402. https://doi.org/10.1101/gr.275723.121
doi: 10.1101/gr.275723.121
pubmed: 34949670
pmcid: 8805725
Mouse Genome Sequencing Consortium, Waterston RH, Lindblad-Toh K et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562. https://doi.org/10.1038/nature01262
doi: 10.1038/nature01262
Nakamura M, Gao Y, Dominguez AA, Qi LS (2021) CRISPR technologies for precise epigenome editing. Nat Cell Biol 23:11–22. https://doi.org/10.1038/s41556-020-00620-7
doi: 10.1038/s41556-020-00620-7
pubmed: 33420494
Nasser J, Bergman DT, Fulco CP et al (2021) Genome-wide enhancer maps link risk variants to disease genes. Nature 593:238–243. https://doi.org/10.1038/s41586-021-03446-x
doi: 10.1038/s41586-021-03446-x
pubmed: 33828297
pmcid: 9153265
Neumayr C, Pagani M, Stark A, Arnold CD (2019) STARR-seq and UMI-STARR-seq: assessing enhancer activities for genome-wide-, high-, and low-complexity candidate libraries. Curr Protoc Mol Biol 128:e105. https://doi.org/10.1002/cpmb.105
doi: 10.1002/cpmb.105
pubmed: 31503413
pmcid: 9286403
Ngan CY, Wong CH, Tjong H et al (2020) Chromatin interaction analyses elucidate the roles of PRC2-bound silencers in mouse development. Nat Genet 52:264–272. https://doi.org/10.1038/s41588-020-0581-x
doi: 10.1038/s41588-020-0581-x
pubmed: 32094912
pmcid: 7869692
Nguyen CT, Gonzales FA, Jones PA (2001) Altered chromatin structure associated with methylation-induced gene silencing in cancer cells: correlation of accessibility, methylation, MeCP2 binding and acetylation. Nucleic Acids Res 29:4598–4606. https://doi.org/10.1093/nar/29.22.4598
doi: 10.1093/nar/29.22.4598
pubmed: 11713309
pmcid: 92514
Nicetto D, Zaret KS (2019) Role of H3K9me3 heterochromatin in cell identity establishment and maintenance. Curr Opin Genet Dev 55:1–10. https://doi.org/10.1016/j.gde.2019.04.013
doi: 10.1016/j.gde.2019.04.013
pubmed: 31103921
pmcid: 6759373
Nikolov DB, Burley SK (1997) RNA polymerase II transcription initiation: a structural view. Proc Natl Acad Sci USA 94:15–22. https://doi.org/10.1073/pnas.94.1.15
doi: 10.1073/pnas.94.1.15
pubmed: 8990153
pmcid: 33652
O’Leary NA, Wright MW, Brister JR et al (2016) Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res 44:D733–D745. https://doi.org/10.1093/nar/gkv1189
doi: 10.1093/nar/gkv1189
pubmed: 26553804
Ogbourne S, Antalis TM (1998) Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes. Biochem J 331(Pt 1):1–14. https://doi.org/10.1042/bj3310001
doi: 10.1042/bj3310001
pubmed: 9512455
pmcid: 1219314
Ong C-T, Corces VG (2014) CTCF: an architectural protein bridging genome topology and function. Nat Rev Genet 15:234–246. https://doi.org/10.1038/nrg3663
doi: 10.1038/nrg3663
pubmed: 24614316
pmcid: 4610363
Palazzo AF, Gregory TR (2014) The case for junk DNA. PLoS Genet 10:e1004351. https://doi.org/10.1371/journal.pgen.1004351
doi: 10.1371/journal.pgen.1004351
pubmed: 24809441
pmcid: 4014423
Pang B, Snyder MP (2020) Systematic identification of silencers in human cells. Nat Genet 52:254–263. https://doi.org/10.1038/s41588-020-0578-5
doi: 10.1038/s41588-020-0578-5
pubmed: 32094911
pmcid: 7148122
Parelho V, Hadjur S, Spivakov M et al (2008) Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell 132:422–433. https://doi.org/10.1016/j.cell.2008.01.011
doi: 10.1016/j.cell.2008.01.011
pubmed: 18237772
Park PJ (2009) ChIP–seq: advantages and challenges of a maturing technology. Nat Rev Genet 10:669–680. https://doi.org/10.1038/nrg2641
doi: 10.1038/nrg2641
pubmed: 19736561
pmcid: 3191340
Parker SCJ, Hansen L, Abaan HO et al (2009) Local DNA topography correlates with functional noncoding regions of the human genome. Science 324:389–392. https://doi.org/10.1126/science.1169050
doi: 10.1126/science.1169050
pubmed: 19286520
pmcid: 2749491
Patikoglou GA, Kim JL, Sun L et al (1999) TATA element recognition by the TATA box-binding protein has been conserved throughout evolution. Genes Dev 13:3217–3230. https://doi.org/10.1101/gad.13.24.3217
doi: 10.1101/gad.13.24.3217
pubmed: 10617571
pmcid: 317201
Patwardhan RP, Hiatt JB, Witten DM et al (2012) Massively parallel functional dissection of mammalian enhancers in vivo. Nat Biotechnol 30:265–270. https://doi.org/10.1038/nbt.2136
doi: 10.1038/nbt.2136
pubmed: 22371081
pmcid: 3402344
Paulsen MT, Veloso A, Prasad J et al (2013) Coordinated regulation of synthesis and stability of RNA during the acute TNF-induced proinflammatory response. Proc Natl Acad Sci U S A 110:2240–2245. https://doi.org/10.1073/pnas.1219192110
doi: 10.1073/pnas.1219192110
pubmed: 23345452
pmcid: 3568384
Pennacchio LA, Ahituv N, Moses AM et al (2006) In vivo enhancer analysis of human conserved non-coding sequences. Nature 444:499–502. https://doi.org/10.1038/nature05295
doi: 10.1038/nature05295
pubmed: 17086198
Pennacchio LA, Bickmore W, Dean A et al (2013) Enhancers: five essential questions. Nat Rev Genet 14:288–295. https://doi.org/10.1038/nrg3458
doi: 10.1038/nrg3458
pubmed: 23503198
pmcid: 4445073
Pheasant M, Mattick JS (2007) Raising the estimate of functional human sequences. Genome Res 17:1245–1253. https://doi.org/10.1101/gr.6406307
doi: 10.1101/gr.6406307
pubmed: 17690206
Phillips JE, Corces VG (2009) CTCF: master weaver of the genome. Cell 137:1194–1211. https://doi.org/10.1016/j.cell.2009.06.001
doi: 10.1016/j.cell.2009.06.001
pubmed: 19563753
pmcid: 3040116
Pickar-Oliver A, Gersbach CA (2019) The next generation of CRISPR–Cas technologies and applications. Nat Rev Mol Cell Biol 20:490–507. https://doi.org/10.1038/s41580-019-0131-5
doi: 10.1038/s41580-019-0131-5
pubmed: 31147612
pmcid: 7079207
Pickrell JK (2014) Joint analysis of functional genomic data and genome-wide association studies of 18 human traits. Am J Hum Genet 94:559–573. https://doi.org/10.1016/j.ajhg.2014.03.004
doi: 10.1016/j.ajhg.2014.03.004
pubmed: 24702953
pmcid: 3980523
Ponjavic J, Lenhard B, Kai C et al (2006) Transcriptional and structural impact of TATA-initiation site spacing in mammalian core promoters. Genome Biol 7:R78. https://doi.org/10.1186/gb-2006-7-8-R78
doi: 10.1186/gb-2006-7-8-R78
pubmed: 16916456
pmcid: 1779604
Ponting CP, Hardison RC (2011) What fraction of the human genome is functional? Genome Res 21:1769–1776. https://doi.org/10.1101/gr.116814.110
doi: 10.1101/gr.116814.110
pubmed: 21875934
pmcid: 3205562
Preissl S, Gaulton KJ, Ren B (2022) Characterizing cis-regulatory elements using single-cell epigenomics. Nat Rev Genet. https://doi.org/10.1038/s41576-022-00509-1
doi: 10.1038/s41576-022-00509-1
pubmed: 35840754
Pugazhenthi S, Wang M, Pham S et al (2011) Downregulation of CREB expression in Alzheimer’s brain and in Aβ-treated rat hippocampal neurons. Mol Neurodegener 6:60. https://doi.org/10.1186/1750-1326-6-60
doi: 10.1186/1750-1326-6-60
pubmed: 21854604
pmcid: 3174124
Pulakanti K, Pinello L, Stelloh C et al (2013) Enhancer transcribed RNAs arise from hypomethylated, Tet-occupied genomic regions. Epigenetics 8:1303–1320. https://doi.org/10.4161/epi.26597
doi: 10.4161/epi.26597
pubmed: 24135681
pmcid: 3933491
Quang D, Xie X (2016) DanQ: a hybrid convolutional and recurrent deep neural network for quantifying the function of DNA sequences. Nucleic Acids Res 44:e107. https://doi.org/10.1093/nar/gkw226
doi: 10.1093/nar/gkw226
pubmed: 27084946
pmcid: 4914104
Quang D, Xie X (2019) FactorNet: A deep learning framework for predicting cell type specific transcription factor binding from nucleotide-resolution sequential data. Methods 166:40–47. https://doi.org/10.1016/j.ymeth.2019.03.020
doi: 10.1016/j.ymeth.2019.03.020
pubmed: 30922998
pmcid: 6708499
Raab JR, Kamakaka RT (2010) Insulators and promoters: closer than we think. Nat Rev Genet 11:439–446. https://doi.org/10.1038/nrg2765
doi: 10.1038/nrg2765
pubmed: 20442713
pmcid: 3477808
Rang FJ, Kloosterman WP, de Ridder J (2018) From squiggle to basepair: computational approaches for improving nanopore sequencing read accuracy. Genome Biol 19:90. https://doi.org/10.1186/s13059-018-1462-9
doi: 10.1186/s13059-018-1462-9
pubmed: 30005597
pmcid: 6045860
Rao SSP, Huntley MH, Durand NC et al (2014) A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159:1665–1680. https://doi.org/10.1016/j.cell.2014.11.021
doi: 10.1016/j.cell.2014.11.021
pubmed: 25497547
pmcid: 5635824
Ravarani CNJ, Flock T, Chavali S et al (2020) Molecular determinants underlying functional innovations of TBP and their impact on transcription initiation. Nat Commun 11:2384. https://doi.org/10.1038/s41467-020-16182-z
doi: 10.1038/s41467-020-16182-z
pubmed: 32404905
pmcid: 7221094
Roadmap Epigenomics Consortium, Kundaje A, Meuleman W et al (2015) Integrative analysis of 111 reference human epigenomes. Nature 518:317–330. https://doi.org/10.1038/nature14248
doi: 10.1038/nature14248
pmcid: 4530010
Routhier E, Mozziconacci J (2022) Genomics enters the deep learning era. PeerJ 10:e13613. https://doi.org/10.7717/peerj.13613
doi: 10.7717/peerj.13613
pubmed: 35769139
pmcid: 9235815
Sanyal A, Lajoie BR, Jain G, Dekker J (2012) The long-range interaction landscape of gene promoters. Nature 489:109–113. https://doi.org/10.1038/nature11279
doi: 10.1038/nature11279
pubmed: 22955621
pmcid: 3555147
Sartorelli V, Lauberth SM (2020) Enhancer RNAs are an important regulatory layer of the epigenome. Nat Struct Mol Biol 27:521–528. https://doi.org/10.1038/s41594-020-0446-0
doi: 10.1038/s41594-020-0446-0
pubmed: 32514177
pmcid: 7343394
Saxonov S, Berg P, Brutlag DL (2006) A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci USA 103:1412–1417. https://doi.org/10.1073/pnas.0510310103
doi: 10.1073/pnas.0510310103
pubmed: 16432200
pmcid: 1345710
Schep AN, Buenrostro JD, Denny SK et al (2015) Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions. Genome Res 25:1757–1770. https://doi.org/10.1101/gr.192294.115
doi: 10.1101/gr.192294.115
pubmed: 26314830
pmcid: 4617971
Schlesinger F, Smith AD, Gingeras TR et al (2013) De novo DNA demethylation and noncoding transcription define active intergenic regulatory elements. Genome Res 23:1601–1614. https://doi.org/10.1101/gr.157271.113
doi: 10.1101/gr.157271.113
pubmed: 23811145
pmcid: 3787258
Schoenherr CJ, Anderson DJ (1995) The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science 267:1360–1363. https://doi.org/10.1126/science.7871435
doi: 10.1126/science.7871435
pubmed: 7871435
Schoggins JW (2019) Interferon-stimulated genes: what do they all do? Annu Rev Virol 6:567–584. https://doi.org/10.1146/annurev-virology-092818-015756
doi: 10.1146/annurev-virology-092818-015756
pubmed: 31283436
Schwessinger R, Gosden M, Downes D et al (2020) DeepC: predicting 3D genome folding using megabase-scale transfer learning. Nat Methods 17:1118–1124. https://doi.org/10.1038/s41592-020-0960-3
doi: 10.1038/s41592-020-0960-3
pubmed: 33046896
pmcid: 7610627
Seale K, Horvath S, Teschendorff A et al (2022) Making sense of the ageing methylome. Nat Rev Genet 23:585–605. https://doi.org/10.1038/s41576-022-00477-6
doi: 10.1038/s41576-022-00477-6
pubmed: 35501397
Shaywitz AJ, Greenberg ME (1999) CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 68:821–861. https://doi.org/10.1146/annurev.biochem.68.1.821
doi: 10.1146/annurev.biochem.68.1.821
pubmed: 10872467
Shukla S, Kavak E, Gregory M et al (2011) CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature 479:74–79. https://doi.org/10.1038/nature10442
doi: 10.1038/nature10442
pubmed: 21964334
pmcid: 7398428
Siegfried Z, Eden S, Mendelsohn M et al (1999) DNA methylation represses transcription in vivo. Nat Genet 22:203–206. https://doi.org/10.1038/9727
doi: 10.1038/9727
pubmed: 10369268
Silverman MN, Sternberg EM (2012) Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Ann N Y Acad Sci 1261:55–63. https://doi.org/10.1111/j.1749-6632.2012.06633.x
doi: 10.1111/j.1749-6632.2012.06633.x
pubmed: 22823394
pmcid: 3572859
Simeonov DR, Gowen BG, Boontanrart M et al (2017) Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature 549:111–115. https://doi.org/10.1038/nature23875
doi: 10.1038/nature23875
pubmed: 28854172
pmcid: 5675716
Sims RJ 3rd, Mandal SS, Reinberg D (2004) Recent highlights of RNA-polymerase-II-mediated transcription. Curr Opin Cell Biol 16:263–271. https://doi.org/10.1016/j.ceb.2004.04.004
doi: 10.1016/j.ceb.2004.04.004
pubmed: 15145350
Snetkova V, Ypsilanti AR, Akiyama JA et al (2021) Ultraconserved enhancer function does not require perfect sequence conservation. Nat Genet 53:521–528. https://doi.org/10.1038/s41588-021-00812-3
doi: 10.1038/s41588-021-00812-3
pubmed: 33782603
pmcid: 8038972
Snetkova V, Pennacchio LA, Visel A, Dickel DE (2022) Perfect and imperfect views of ultraconserved sequences. Nat Rev Genet 23:182–194. https://doi.org/10.1038/s41576-021-00424-x
doi: 10.1038/s41576-021-00424-x
pubmed: 34764456
Sohn K-A, Ho JWK, Djordjevic D et al (2015) hiHMM: Bayesian non-parametric joint inference of chromatin state maps. Bioinformatics 31:2066–2074. https://doi.org/10.1093/bioinformatics/btv117
doi: 10.1093/bioinformatics/btv117
pubmed: 25725496
pmcid: 4481846
Song H, Liu Y, Tan Y et al (2022) Recurrent non-coding somatic and germline WT1 variants converge to disrupt MYB binding in acute promyelocytic leukemia. Blood J Am Soc Hematol 140(10):1132–1144. https://doi.org/10.1182/blood.2021014945
doi: 10.1182/blood.2021014945
Spitz F (2016) Gene regulation at a distance: from remote enhancers to 3D regulatory ensembles. Semin Cell Dev Biol 57:57–67. https://doi.org/10.1016/j.semcdb.2016.06.017
doi: 10.1016/j.semcdb.2016.06.017
pubmed: 27364700
Stadler MB, Murr R, Burger L et al (2011) DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 480:490–495. https://doi.org/10.1038/nature10716
doi: 10.1038/nature10716
pubmed: 22170606
Steven A, Friedrich M, Jank P et al (2020) What turns CREB on? And off? And why does it matter? Cell Mol Life Sci 77:4049–4067. https://doi.org/10.1007/s00018-020-03525-8
doi: 10.1007/s00018-020-03525-8
pubmed: 32347317
pmcid: 7532970
Su X-J, Shen B-D, Wang K et al (2022) Roles of the neuron-restrictive silencer factor in the pathophysiological process of the central nervous system. Front Cell Dev Biol 10:834620. https://doi.org/10.3389/fcell.2022.834620
doi: 10.3389/fcell.2022.834620
pubmed: 35300407
pmcid: 8921553
Symmons O, Uslu VV, Tsujimura T et al (2014) Functional and topological characteristics of mammalian regulatory domains. Genome Res 24:390–400. https://doi.org/10.1101/gr.163519.113
doi: 10.1101/gr.163519.113
pubmed: 24398455
pmcid: 3941104
Takahashi H, Lassmann T, Murata M, Carninci P (2012) 5’ end-centered expression profiling using cap-analysis gene expression and next-generation sequencing. Nat Protoc 7:542–561. https://doi.org/10.1038/nprot.2012.005
doi: 10.1038/nprot.2012.005
pubmed: 22362160
pmcid: 4094379
Thompson R, Chan C (2018) NRSF and its epigenetic effectors: new treatments for neurological disease. Brain Sci 8:226. https://doi.org/10.3390/brainsci8120226
doi: 10.3390/brainsci8120226
pubmed: 30572571
pmcid: 6316267
Thurman RE, Rynes E, Humbert R et al (2012) The accessible chromatin landscape of the human genome. Nature 489:75–82. https://doi.org/10.1038/nature11232
doi: 10.1038/nature11232
pubmed: 22955617
pmcid: 3721348
Tippens ND, Liang J, Leung AK-Y et al (2020) Transcription imparts architecture, function and logic to enhancer units. Nat Genet 52:1067–1075. https://doi.org/10.1038/s41588-020-0686-2
doi: 10.1038/s41588-020-0686-2
pubmed: 32958950
pmcid: 7541647
Tiwari VK, McGarvey KM, Licchesi JDF et al (2008) PcG proteins, DNA methylation, and gene repression by chromatin looping. PLoS Biol 6:2911–2927. https://doi.org/10.1371/journal.pbio.0060306
doi: 10.1371/journal.pbio.0060306
pubmed: 19053175
Tsai P-F, Dell’Orso S, Rodriguez J et al (2018) A muscle-specific enhancer RNA mediates cohesin recruitment and regulates transcription in trans. Mol Cell 71:129-141.e8. https://doi.org/10.1016/j.molcel.2018.06.008
doi: 10.1016/j.molcel.2018.06.008
pubmed: 29979962
pmcid: 6082425
Tuan D, Kong S, Hu K (1992) Transcription of the hypersensitive site HS2 enhancer in erythroid cells. Proc Natl Acad Sci U S A 89:11219–11223. https://doi.org/10.1073/pnas.89.23.11219
doi: 10.1073/pnas.89.23.11219
pubmed: 1454801
pmcid: 50521
Unnikrishnan A, Hadad N, Masser DR et al (2018) Revisiting the genomic hypomethylation hypothesis of aging. Ann N Y Acad Sci 1418:69–79. https://doi.org/10.1111/nyas.13533
doi: 10.1111/nyas.13533
pubmed: 29363785
pmcid: 5934293
van der Velde A, Fan K, Tsuji J et al (2021) Annotation of chromatin states in 66 complete mouse epigenomes during development. Commun Biol 4:239. https://doi.org/10.1038/s42003-021-01756-4
doi: 10.1038/s42003-021-01756-4
pubmed: 33619351
pmcid: 7900196
Varley KE, Gertz J, Bowling KM et al (2013) Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res 23:555–567. https://doi.org/10.1101/gr.147942.112
doi: 10.1101/gr.147942.112
pubmed: 23325432
pmcid: 3589544
Visel A, Minovitsky S, Dubchak I, Pennacchio LA (2006) VISTA Enhancer Browser—a database of tissue-specific human enhancers. Nucleic Acids Res 35:D88–D92. https://doi.org/10.1093/nar/gkl822
doi: 10.1093/nar/gkl822
pubmed: 17130149
pmcid: 1716724
Visel A, Prabhakar S, Akiyama JA et al (2008) Ultraconservation identifies a small subset of extremely constrained developmental enhancers. Nat Genet 40:158–160. https://doi.org/10.1038/ng.2007.55
doi: 10.1038/ng.2007.55
pubmed: 18176564
pmcid: 2647775
Wang H, La Russa M, Qi LS (2016) CRISPR/Cas9 in genome editing and beyond. Annu Rev Biochem 85:227–264. https://doi.org/10.1146/annurev-biochem-060815-014607
doi: 10.1146/annurev-biochem-060815-014607
pubmed: 27145843
Wang H, Xu J, Lazarovici P et al (2018) cAMP response element-binding protein (CREB): a possible signaling molecule link in the pathophysiology of schizophrenia. Front Mol Neurosci 11:255. https://doi.org/10.3389/fnmol.2018.00255
doi: 10.3389/fnmol.2018.00255
pubmed: 30214393
pmcid: 6125665
Weidemüller P, Kholmatov M, Petsalaki E, Zaugg JB (2021) Transcription factors: Bridge between cell signaling and gene regulation. Proteomics 21:e2000034. https://doi.org/10.1002/pmic.202000034
doi: 10.1002/pmic.202000034
pubmed: 34314098
Weikum ER, Knuesel MT, Ortlund EA, Yamamoto KR (2017) Glucocorticoid receptor control of transcription: precision and plasticity via allostery. Nat Rev Mol Cell Biol 18:159–174
doi: 10.1038/nrm.2016.152
pubmed: 28053348
pmcid: 6257982
Wendt KS, Yoshida K, Itoh T et al (2008) Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature 451:796–801. https://doi.org/10.1038/nature06634
doi: 10.1038/nature06634
pubmed: 18235444
Whalen S, Schreiber J, Noble WS, Pollard KS (2022) Navigating the pitfalls of applying machine learning in genomics. Nat Rev Genet 23:169–181. https://doi.org/10.1038/s41576-021-00434-9
doi: 10.1038/s41576-021-00434-9
pubmed: 34837041
Wick RR, Judd LM, Holt KE (2018) Deepbinner: Demultiplexing barcoded Oxford Nanopore reads with deep convolutional neural networks. PLoS Comput Biol 14:e1006583. https://doi.org/10.1371/journal.pcbi.1006583
doi: 10.1371/journal.pcbi.1006583
pubmed: 30458005
pmcid: 6245502
Wick RR, Judd LM, Holt KE (2019) Performance of neural network basecalling tools for Oxford Nanopore sequencing. Genome Biol 20:129. https://doi.org/10.1186/s13059-019-1727-y
doi: 10.1186/s13059-019-1727-y
pubmed: 31234903
pmcid: 6591954
Wilbanks EG, Facciotti MT (2010) Evaluation of algorithm performance in ChIP-seq peak detection. PLoS ONE 5:e11471. https://doi.org/10.1371/journal.pone.0011471
doi: 10.1371/journal.pone.0011471
pubmed: 20628599
pmcid: 2900203
Wilson VL, Smith RA, Ma S, Cutler RG (1987) Genomic 5-methyldeoxycytidine decreases with age. J Biol Chem 262:9948–9951
doi: 10.1016/S0021-9258(18)61057-9
pubmed: 3611071
Woolfe A, Goodson M, Goode DK et al (2005) Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol 3:e7. https://doi.org/10.1371/journal.pbio.0030007
doi: 10.1371/journal.pbio.0030007
pubmed: 15630479
Wu X, Sharp PA (2013) Divergent transcription: a driving force for new gene origination? Cell 155:990–996. https://doi.org/10.1016/j.cell.2013.10.048
doi: 10.1016/j.cell.2013.10.048
pubmed: 24267885
pmcid: 3899942
Wyman D, Balderrama-Gutierrez G, Reese F et al (2020) A technology-agnostic long-read analysis pipeline for transcriptome discovery and quantification. bioRxiv 672931
Yang J, Corces VG (2011) Chromatin insulators: a role in nuclear organization and gene expression. Adv Cancer Res 110:43–76. https://doi.org/10.1016/B978-0-12-386469-7.00003-7
doi: 10.1016/B978-0-12-386469-7.00003-7
pubmed: 21704228
pmcid: 3175007
Yao L, Berman BP, Farnham PJ (2015) Demystifying the secret mission of enhancers: linking distal regulatory elements to target genes. Crit Rev Biochem Mol Biol 50:550–573. https://doi.org/10.3109/10409238.2015.1087961
doi: 10.3109/10409238.2015.1087961
pubmed: 26446758
pmcid: 4666684
Yao L, Liang J, Ozer A et al (2022) A comparison of experimental assays and analytical methods for genome-wide identification of active enhancers. Nat Biotechnol 40:1056–1065. https://doi.org/10.1038/s41587-022-01211-7
doi: 10.1038/s41587-022-01211-7
pubmed: 35177836
pmcid: 9288987
Yin Y, Morgunova E, Jolma A et al (2017) Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science. https://doi.org/10.1126/science.aaj2239
doi: 10.1126/science.aaj2239
pubmed: 29242318
pmcid: 6384012
Yuan H, Kelley DR (2022) scBasset: sequence-based modeling of single-cell ATAC-seq using convolutional neural networks. Nat Methods. https://doi.org/10.1038/s41592-022-01562-8
doi: 10.1038/s41592-022-01562-8
pubmed: 35941239
Zabidi MA, Stark A (2016) Regulatory enhancer–core-promoter communication via transcription factors and cofactors. Trends Genet 32:801–814. https://doi.org/10.1016/j.tig.2016.10.003
doi: 10.1016/j.tig.2016.10.003
pubmed: 27816209
pmcid: 6795546
Zaret KS (2020) Pioneer Transcription factors initiating gene network changes. Annu Rev Genet 54:367–385. https://doi.org/10.1146/annurev-genet-030220-015007
doi: 10.1146/annurev-genet-030220-015007
pubmed: 32886547
pmcid: 7900943
Zaret KS, Carroll JS (2011) Pioneer transcription factors: establishing competence for gene expression. Genes Dev 25:2227–2241. https://doi.org/10.1101/gad.176826.111
doi: 10.1101/gad.176826.111
pubmed: 22056668
pmcid: 3219227
Zemach A, McDaniel IE, Silva P, Zilberman D (2010) Genome-wide evolutionary analysis of eukaryotic DNA methylation. Science 328:916–919. https://doi.org/10.1126/science.1186366
doi: 10.1126/science.1186366
pubmed: 20395474
Zhang Y, Mahony S (2019) Direct prediction of regulatory elements from partial data without imputation. PLoS Comput Biol 15:e1007399. https://doi.org/10.1371/journal.pcbi.1007399
doi: 10.1371/journal.pcbi.1007399
pubmed: 31682602
pmcid: 6855516
Zhang Y, Liu T, Meyer CA et al (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9:R137. https://doi.org/10.1186/gb-2008-9-9-r137
doi: 10.1186/gb-2008-9-9-r137
pubmed: 18798982
pmcid: 2592715
Zhang Y, Wu W, Cheng Y et al (2009) Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1. Nucleic Acids Res 37:7024–7038. https://doi.org/10.1093/nar/gkp747
doi: 10.1093/nar/gkp747
pubmed: 19767611
pmcid: 2790884
Zhang F, Wen Y, Guo X (2014) CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet 23:R40–R46. https://doi.org/10.1093/hmg/ddu125
doi: 10.1093/hmg/ddu125
pubmed: 24651067
Zhang Y, An L, Yue F, Hardison RC (2016) Jointly characterizing epigenetic dynamics across multiple human cell types. Nucleic Acids Res 44:6721–6731. https://doi.org/10.1093/nar/gkw278
doi: 10.1093/nar/gkw278
pubmed: 27095202
pmcid: 5772166
Zhao Z, Tavoosidana G, Sjölinder M et al (2006) Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nat Genet 38:1341–1347. https://doi.org/10.1038/ng1891
doi: 10.1038/ng1891
pubmed: 17033624
Zhou J, Troyanskaya OG (2015) Predicting effects of noncoding variants with deep learning–based sequence model. Nat Methods 12:931–934. https://doi.org/10.1038/nmeth.3547
doi: 10.1038/nmeth.3547
pubmed: 26301843
pmcid: 4768299
Zhu Y, Sun L, Chen Z et al (2013) Predicting enhancer transcription and activity from chromatin modifications. Nucleic Acids Res 41:10032–10043. https://doi.org/10.1093/nar/gkt826
doi: 10.1093/nar/gkt826
pubmed: 24038352
pmcid: 3905895