The HIF complex recruits the histone methyltransferase SET1B to activate specific hypoxia-inducible genes.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
29
09
2020
accepted:
14
05
2021
pubmed:
23
6
2021
medline:
31
8
2021
entrez:
22
6
2021
Statut:
ppublish
Résumé
Hypoxia-inducible transcription factors (HIFs) are fundamental to cellular adaptation to low oxygen levels, but it is unclear how they interact with chromatin and activate their target genes. Here, we use genome-wide mutagenesis to identify genes involved in HIF transcriptional activity, and define a requirement for the histone H3 lysine 4 (H3K4) methyltransferase SET1B. SET1B loss leads to a selective reduction in transcriptional activation of HIF target genes, resulting in impaired cell growth, angiogenesis and tumor establishment in SET1B-deficient xenografts. Mechanistically, we show that SET1B accumulates on chromatin in hypoxia, and is recruited to HIF target genes by the HIF complex. The selective induction of H3K4 trimethylation at HIF target loci is both HIF- and SET1B-dependent and, when impaired, correlates with decreased promoter acetylation and gene expression. Together, these findings show SET1B as a determinant of site-specific histone methylation and provide insight into how HIF target genes are differentially regulated.
Identifiants
pubmed: 34155378
doi: 10.1038/s41588-021-00887-y
pii: 10.1038/s41588-021-00887-y
pmc: PMC7611696
mid: EMS124568
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Setd1A protein, human
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1022-1035Subventions
Organisme : Wellcome Trust
ID : FC001501
Pays : United Kingdom
Organisme : Department of Health
ID : NIHR-RP-2016-06-004
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106241
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001501
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001501
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001501
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001501
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001501
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 215477/Z/19/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106241/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 096956/Z/11/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 096956
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203141/Z/16/Z
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : FC001501
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 215477
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Kaelin, W. G. Jr. & Ratcliffe, P. J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell 30, 393–402 (2008).
pubmed: 18498744
doi: 10.1016/j.molcel.2008.04.009
Semenza, G. L. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci. STKE 2007, cm8 (2007).
pubmed: 17925579
doi: 10.1126/stke.4072007cm8
Epstein, A. C. et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107, 43–54 (2001).
pubmed: 11595184
doi: 10.1016/S0092-8674(01)00507-4
Maxwell, P. H. et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399, 271–275 (1999).
pubmed: 10353251
doi: 10.1038/20459
Ivan, M. et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O
pubmed: 11292862
doi: 10.1126/science.1059817
Bruick, R. K. & McKnight, S. L. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294, 1337–1340 (2001).
pubmed: 11598268
doi: 10.1126/science.1066373
Jaakkola, P. et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292, 468–472 (2001).
pubmed: 11292861
doi: 10.1126/science.1059796
Arany, Z. et al. An essential role for p300/CBP in the cellular response to hypoxia. Proc. Natl Acad. Sci. USA 93, 12969–12973 (1996).
pubmed: 8917528
pmcid: 24030
doi: 10.1073/pnas.93.23.12969
Perez-Perri, J. I. et al. The TIP60 complex is a conserved coactivator of HIF1A. Cell Rep. 16, 37–47 (2016).
pubmed: 27320910
pmcid: 4957981
doi: 10.1016/j.celrep.2016.05.082
Dekanty, A. et al. Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia. PLoS Genet. 6, e1000994 (2010).
pubmed: 20585616
pmcid: 2891703
doi: 10.1371/journal.pgen.1000994
Galbraith, M. D. et al. HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia. Cell 153, 1327–1339 (2013).
pubmed: 23746844
pmcid: 3681429
doi: 10.1016/j.cell.2013.04.048
Batie, M. et al. Hypoxia induces rapid changes to histone methylation and reprograms chromatin. Science 363, 1222–1226 (2019).
pubmed: 30872526
doi: 10.1126/science.aau5870
Chakraborty, A. A. et al. Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate. Science 363, 1217–1222 (2019).
pubmed: 30872525
pmcid: 7336390
doi: 10.1126/science.aaw1026
Lee, J. H., Tate, C. M., You, J. S. & Skalnik, D. G. Identification and characterization of the human Set1B histone H3-Lys4 methyltransferase complex. J. Biol. Chem. 282, 13419–13428 (2007).
pubmed: 17355966
doi: 10.1074/jbc.M609809200
Shilatifard, A. The COMPASS family of histone H3K4 methylases: mechanisms of regulation in development and disease pathogenesis. Annu. Rev. Biochem. 81, 65–95 (2012).
pubmed: 22663077
pmcid: 4010150
doi: 10.1146/annurev-biochem-051710-134100
Burr, S. P. et al. Mitochondrial protein lipoylation and the 2-oxoglutarate dehydrogenase complex controls HIF1alpha stability in aerobic conditions. Cell Metab. 24, 740–752 (2016).
pubmed: 27923773
pmcid: 5106373
doi: 10.1016/j.cmet.2016.09.015
Miles, A. L., Burr, S. P., Grice, G. L. & Nathan, J. A. The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115, control HIF1alpha prolyl hydroxylation by regulating cellular iron levels. eLife 6, e22693 (2017).
Hart, T. et al. High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities. Cell 163, 1515–1526 (2015).
pubmed: 26627737
doi: 10.1016/j.cell.2015.11.015
Kim, J., Hake, S. B. & Roeder, R. G. The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activator interactions. Mol. Cell 20, 759–770 (2005).
pubmed: 16337599
doi: 10.1016/j.molcel.2005.11.012
Prenzel, T. et al. Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependent monoubiquitination of histone H2B. Cancer Res. 71, 5739–5753 (2011).
pubmed: 21862633
doi: 10.1158/0008-5472.CAN-11-1896
Zhang, X. et al. Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4. Genes Dev. 19, 827–839 (2005).
pubmed: 15805470
pmcid: 1074320
doi: 10.1101/gad.1286005
Maxwell, P. H. et al. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc. Natl Acad. Sci. USA 94, 8104–8109 (1997).
pubmed: 9223322
pmcid: 21564
doi: 10.1073/pnas.94.15.8104
Ryan, H. E. et al. Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res. 60, 4010–4015 (2000).
pubmed: 10945599
Bertout, J. A., Patel, S. A. & Simon, M. C. The impact of O2 availability on human cancer. Nat. Rev. Cancer 8, 967–975 (2008).
pubmed: 18987634
pmcid: 3140692
doi: 10.1038/nrc2540
Kung, A. L., Wang, S., Klco, J. M., Kaelin, W. G. & Livingston, D. M. Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat. Med. 6, 1335–1340 (2000).
pubmed: 11100117
doi: 10.1038/82146
Wang, L. et al. A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism. Genes Dev. 31, 2056–2066 (2017).
pubmed: 29138278
pmcid: 5733497
doi: 10.1101/gad.306092.117
Tang, Z. et al. SET1 and p300 act synergistically, through coupled histone modifications, in transcriptional activation by p53. Cell 154, 297–310 (2013).
pubmed: 23870121
pmcid: 4023349
doi: 10.1016/j.cell.2013.06.027
Wang, Z. et al. Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138, 1019–1031 (2009).
pubmed: 19698979
pmcid: 2750862
doi: 10.1016/j.cell.2009.06.049
Crump, N. T. et al. Dynamic acetylation of all lysine-4 trimethylated histone H3 is evolutionarily conserved and mediated by p300/CBP. Proc. Natl Acad. Sci. USA 108, 7814–7819 (2011).
pubmed: 21518915
pmcid: 3093510
doi: 10.1073/pnas.1100099108
Zhang, T., Cooper, S. & Brockdorff, N. The interplay of histone modifications – writers that read. EMBO Rep. 16, 1467–1481 (2015).
pubmed: 26474904
pmcid: 4641500
doi: 10.15252/embr.201540945
Sun, Z. W. & Allis, C. D. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418, 104–108 (2002).
pubmed: 12077605
doi: 10.1038/nature00883
Pavri, R. et al. Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell 125, 703–717 (2006).
pubmed: 16713563
doi: 10.1016/j.cell.2006.04.029
Zhu, B. et al. Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol. Cell 20, 601–611 (2005).
pubmed: 16307923
doi: 10.1016/j.molcel.2005.09.025
Chen, Y. et al. ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis. J. Clin. Invest. 128, 1937–1955 (2018).
pubmed: 29629903
pmcid: 5919820
doi: 10.1172/JCI95089
Brici, D. et al. Setd1b, encoding a histone 3 lysine 4 methyltransferase, is a maternal effect gene required for the oogenic gene expression program. Development 144, 2606–2617 (2017).
pubmed: 28619824
Schmidt, K. et al. The H3K4 methyltransferase Setd1b is essential for hematopoietic stem and progenitor cell homeostasis in mice. eLife 7, e27157 (2018).
Schodel, J. et al. High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. Blood 117, e207–e217 (2011).
pubmed: 21447827
pmcid: 3374576
doi: 10.1182/blood-2010-10-314427
Smythies, J. A. et al. Inherent DNA-binding specificities of the HIF-1α and HIF-2α transcription factors in chromatin. EMBO Rep. 20, e46401 (2019).
Qiu, B. et al. HIF2α-dependent lipid storage promotes endoplasmic reticulum homeostasis in clear-cell renal cell carcinoma. Cancer Disco. 5, 652–667 (2015).
doi: 10.1158/2159-8290.CD-14-1507
Semenza, G. L. Physiology meets biophysics: visualizing the interaction of hypoxia-inducible factor 1 alpha with p300 and CBP. Proc. Natl Acad. Sci. USA 99, 11570–11572 (2002).
pubmed: 12186981
pmcid: 129309
doi: 10.1073/pnas.192442299
Douillet, D. et al. Uncoupling histone H3K4 trimethylation from developmental gene expression via an equilibrium of COMPASS, Polycomb and DNA methylation. Nat. Genet. 52, 615–625 (2020).
pubmed: 32393859
pmcid: 7790509
doi: 10.1038/s41588-020-0618-1
Fang, L. et al. SET1A-mediated mono-methylation at K342 regulates YAP activation by blocking its nuclear export and promotes tumorigenesis. Cancer Cell 34, 103–118.e9 (2018).
pubmed: 30008322
doi: 10.1016/j.ccell.2018.06.002
Luo, W., Chang, R., Zhong, J., Pandey, A. & Semenza, G. L. Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression. Proc. Natl Acad. Sci. 109, E3367–E3376 (2012).
pubmed: 23129632
pmcid: 3523832
doi: 10.1073/pnas.1217394109
Chen, W. et al. Targeting renal cell carcinoma with a HIF-2 antagonist. Nature 539, 112–117 (2016).
pubmed: 27595394
pmcid: 5340502
doi: 10.1038/nature19796
Scheuermann, T. H. et al. Allosteric inhibition of hypoxia inducible factor-2 with small molecules. Nat. Chem. Biol. 9, 271–276 (2013).
pubmed: 23434853
pmcid: 3604136
doi: 10.1038/nchembio.1185
Cho, H. et al. On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. Nature 539, 107–111 (2016).
pubmed: 27595393
pmcid: 5499381
doi: 10.1038/nature19795
Courtney, K. D. et al. HIF-2 complex dissociation, target inhibition, and acquired resistance with PT2385, a first-in-class HIF-2 inhibitor, in patients with clear cell renal cell carcinoma. Clin. Cancer Res. 26, 793–803 (2020).
pubmed: 31727677
doi: 10.1158/1078-0432.CCR-19-1459
Wykoff, C. C., Pugh, C. W., Maxwell, P. H., Harris, A. L. & Ratcliffe, P. J. Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling. Oncogene 19, 6297–6305 (2000).
pubmed: 11175344
doi: 10.1038/sj.onc.1204012
Demaison, C. et al. High-level transduction and gene expression in hematopoietic repopulating cells using a human immunodeficiency [correction of imunodeficiency] virus type 1-based lentiviral vector containing an internal spleen focus forming virus promoter. Hum. Gene Ther. 13, 803–813 (2002).
pubmed: 11975847
doi: 10.1089/10430340252898984
Bailey, P. S. J. et al. ABHD11 maintains 2-oxoglutarate metabolism by preserving functional lipoylation of the 2-oxoglutarate dehydrogenase complex. Nat. Commun. 11, 4046 (2020).
pubmed: 32792488
pmcid: 7426941
doi: 10.1038/s41467-020-17862-6
Schödel, J. et al. High-resolution genome-wide mapping of HIF-binding sites by ChIP–seq. Blood 117, e207–e217 (2011).
pubmed: 21447827
pmcid: 3374576
doi: 10.1182/blood-2010-10-314427
Salama, R. et al. Heterogeneous effects of direct hypoxia pathway activation in kidney cancer. PLoS ONE 10, e0134645 (2015).
pubmed: 26262842
pmcid: 4532367
doi: 10.1371/journal.pone.0134645
Shen, L., Shao, N., Liu, X. & Nestler, E. ngs.plot: quick mining and visualization of next-generation sequencing data by integrating genomic databases. BMC Genomics 15, 284 (2014).
pubmed: 24735413
pmcid: 4028082
doi: 10.1186/1471-2164-15-284
Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24–26 (2011).
pubmed: 21221095
pmcid: 3346182
doi: 10.1038/nbt.1754
Hower, V., Evans, S. N. & Pachter, L. Shape-based peak identification for ChIP–Seq. BMC Bioinf. 12, 15 (2011).
doi: 10.1186/1471-2105-12-15
Stark, R. & Brown, G. DiffBind: Differential binding analysis of ChIP–Seq peak data (2011); http://bioconductor.org/packages/release/bioc/html/DiffBind.html
Dale, R. K., Pedersen, B. S. & Quinlan, A. R. Pybedtools: a flexible Python library for manipulating genomic datasets and annotations. Bioinformatics 27, 3423–3424 (2011).
pubmed: 21949271
pmcid: 3232365
doi: 10.1093/bioinformatics/btr539
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
pubmed: 19505943
pmcid: 2723002
doi: 10.1093/bioinformatics/btp352
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
pubmed: 16199517
pmcid: 1239896
doi: 10.1073/pnas.0506580102
Mootha, V. K. et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273 (2003).
pubmed: 12808457
doi: 10.1038/ng1180
Leek, R., Grimes, D. R., Harris, A. L. & McIntyre, A. Methods: using three-dimensional culture (spheroids) as an in vitro model of tumour hypoxia. Adv. Exp. Med. Biol. 899, 167–196 (2016).
pubmed: 27325267
doi: 10.1007/978-3-319-26666-4_10
Väyrynen, S. A. et al. Clinical impact and network of determinants of tumour necrosis in colorectal cancer. Br. J. Cancer 114, 1334–1342 (2016).
pubmed: 27195424
pmcid: 4984458
doi: 10.1038/bjc.2016.128
Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017).
pubmed: 29203879
pmcid: 5715110
doi: 10.1038/s41598-017-17204-5
Niemistö, A., Dunmire, V., Yli-Harja, O., Zhang, W. & Shmulevich, I. Robust quantification of in vitro angiogenesis through image analysis. IEEE Trans. Med. Imaging 24, 549–553 (2005).
pubmed: 15822812
doi: 10.1109/TMI.2004.837339
Li, W. et al. MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens. Genome Biol. 15, 554 (2014).
pubmed: 25476604
pmcid: 4290824
doi: 10.1186/s13059-014-0554-4