DNA methylation enzymes and PRC1 restrict B-cell Epstein-Barr virus oncoprotein expression.

Antigens, Viral B-Lymphocytes / virology Burkitt Lymphoma CCAAT-Enhancer-Binding Proteins CRISPR-Cas Systems Cell Cycle Proteins / genetics DNA (Cytosine-5-)-Methyltransferase 1 / metabolism DNA (Cytosine-5-)-Methyltransferases DNA Methylation / physiology Epstein-Barr Virus Nuclear Antigens Gene Expression Regulation, Viral / drug effects Genes, Viral Genome, Viral Herpesvirus 4, Human / drug effects Humans Oncogene Proteins / genetics Ubiquitin-Protein Ligases DNA Methyltransferase 3B

Journal

Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869

Informations de publication

Date de publication:
08 2020
Historique:
received: 11 11 2019
accepted: 16 04 2020
pubmed: 20 5 2020
medline: 18 11 2020
entrez: 20 5 2020
Statut: ppublish

Résumé

To accomplish the remarkable task of lifelong infection, the Epstein-Barr virus (EBV) switches between four viral genome latency and lytic programmes to navigate the B-cell compartment and evade immune responses. The transforming programme, consisting of highly immunogenic EBV nuclear antigen (EBNA) and latent membrane proteins (LMPs), is expressed in newly infected B lymphocytes and in post-transplant lymphomas. On memory cell differentiation and in most EBV-associated Burkitt's lymphomas, all but one viral antigen are repressed for immunoevasion. To gain insights into the epigenetic mechanisms that restrict immunogenic oncoprotein expression, a genome-scale CRISPR-Cas9 screen was performed in EBV and Burkitt's lymphoma cells. Here, we show that the ubiquitin ligase ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1) and its DNA methyltransferase partner DNA methyltransferase I (DNMT1) are critical for the restriction of EBNA and LMP expression. All UHRF1 reader and writer domains were necessary for silencing and DNMT3B was identified as an upstream viral genome CpG methylation initiator. Polycomb repressive complex I exerted a further layer of control over LMP expression, suggesting a second mechanism for latency programme switching. UHRF1, DNMT1 and DNMT3B are upregulated in germinal centre B cells, the Burkitt's lymphoma cell of origin, providing a molecular link between B-cell state and the EBV latency programme. These results suggest rational therapeutic targets to manipulate EBV oncoprotein expression.

Identifiants

DOI: 10.1038/s41564-020-0724-y PMID: 32424339 PMC: PMC7462085
pubmed: 32424339
doi: 10.1038/s41564-020-0724-y
pii: 10.1038/s41564-020-0724-y
pmc: PMC7462085
mid: NIHMS1585639
doi:

Substances chimiques

Antigens, Viral 0
CCAAT-Enhancer-Binding Proteins 0
Cell Cycle Proteins 0
Epstein-Barr Virus Nuclear Antigens 0
Oncogene Proteins 0
PRC1 protein, human 0
DNA (Cytosine-5-)-Methyltransferase 1 EC 2.1.1.37
DNA (Cytosine-5-)-Methyltransferases EC 2.1.1.37
DNMT1 protein, human EC 2.1.1.37
UHRF1 protein, human EC 2.3.2.27
Ubiquitin-Protein Ligases EC 2.3.2.27

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1051-1063

Subventions

Organisme : NCI NIH HHS
ID : R01 CA047006
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA219473
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA228700
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137337
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA047006
Pays : United States

Commentaires et corrections

Type : ErratumIn

Références

Longnecker, R. M., Kieff, E. & Cohen, J. I. in Fields Virology 6th edn, Vol. 1 (Wolters Kluwer Health Adis (ESP), 2013).
Cohen, J. I. Epstein–Barr virus infection. N. Engl. J. Med. 343, 481–492 (2000).
pubmed: 10944566
Thorley-Lawson, D. A. EBV persistence–introducing the virus. Curr. Top. Microbiol. Immunol. 390, 151–209 (2015).
pubmed: 26424647 pmcid: 5125397
Price, A. M. & Luftig, M. A. To be or not IIb: a multi-step process for Epstein–Barr virus latency establishment and consequences for B cell tumorigenesis. PLoS Pathog. 11, e1004656 (2015).
pubmed: 25790223 pmcid: 4366242
Woellmer, A. & Hammerschmidt, W. Epstein–Barr virus and host cell methylation: regulation of latency, replication and virus reactivation. Curr. Opin. Virol. 3, 260–265 (2013).
pubmed: 23567077 pmcid: 3799965
Price, A. M., Messinger, J. & Luftig, M. A. c-Myc represses transcription of Epstein–Barr virus latent membrane protein 1 early after primary B cell infection. J. Virol. 92, e01178-17 (2018).
pubmed: 29118124 pmcid: 5752943
Mrozek-Gorska, P. et al. Epstein–Barr virus reprograms human B lymphocytes immediately in the prelatent phase of infection. Proc. Natl Acad. Sci. USA 116, 16046–16055 (2019).
pubmed: 31341086 pmcid: 6690029
Wang, L. W. et al. Epstein–Barr-virus-induced one-carbon metabolism drives B cell transformation. Cell Metab. 30, 539–555 (2019).
pubmed: 31257153 pmcid: 6720460
Seifert, M., Scholtysik, R. & Kuppers, R. Origin and pathogenesis of B cell lymphomas. Methods Mol. Biol. 971, 1–25 (2013).
pubmed: 23296955
Westhoff Smith, D. & Sugden, B. Potential cellular functions of Epstein–Barr nuclear antigen 1 (EBNA1) of Epstein–Barr virus. Viruses 5, 226–240 (2013).
pubmed: 23325328
Sugden, B. Epstein–Barr virus: the path from association to causality for a ubiquitous human pathogen. PLoS Biol. 12, e1001939 (2014).
pubmed: 25180782 pmcid: 4151957
Schaefer, B. C., Strominger, J. L. & Speck, S. H. Host-cell-determined methylation of specific Epstein–Barr virus promoters regulates the choice between distinct viral latency programs. Mol. Cell. Biol. 17, 364–377 (1997).
pubmed: 8972217 pmcid: 231761
Masucci, M. G. et al. 5-Azacytidine up regulates the expression of Epstein–Barr virus nuclear antigen 2 (EBNA-2) through EBNA-6 and latent membrane protein in the Burkitt’s lymphoma line rael. J. Virol. 63, 3135–3141 (1989).
pubmed: 2470924 pmcid: 250871
Kalla, M., Schmeinck, A., Bergbauer, M., Pich, D. & Hammerschmidt, W. AP-1 homolog BZLF1 of Epstein–Barr virus has two essential functions dependent on the epigenetic state of the viral genome. Proc. Natl Acad. Sci. USA 107, 850–855 (2010).
pubmed: 20080764
Robertson, K. D., Hayward, S. D., Ling, P. D., Samid, D. & Ambinder, R. F. Transcriptional activation of the Epstein–Barr virus latency C promoter after 5-azacytidine treatment: evidence that demethylation at a single CpG site is crucial. Mol. Cell. Biol. 15, 6150–6159 (1995).
pubmed: 7565767 pmcid: 230866
Niller, H. H., Szenthe, K. & Minarovits, J. Epstein–Barr virus–host cell interactions: an epigenetic dialog? Front. Genet. 5, 367 (2014).
pubmed: 25400657 pmcid: 4212275
Hughes, D. J. et al. Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein–Barr virus restricted latency. J. Virol. 86, 1034–1045 (2012).
pubmed: 22072770 pmcid: 3255836
Gregory, C. D., Rowe, M. & Rickinson, A. B. Different Epstein–Barr virus-B cell interactions in phenotypically distinct clones of a Burkitt’s lymphoma cell line. J. Gen. Virol. 71, 1481–1495 (1990).
pubmed: 2165133
Babcock, G. J., Hochberg, D. & Thorley-Lawson, D. A. The expression pattern of Epstein–Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell. Immunity 13, 497–506 (2000).
pubmed: 11070168
Carter, K. L., Cahir-McFarland, E. & Kieff, E. Epstein–Barr virus-induced changes in B-lymphocyte gene expression. J. Virol. 76, 10427–10436 (2002).
pubmed: 12239319 pmcid: 136539
Peng, M. & Lundgren, E. Transient expression of the Epstein–Barr virus LMP1 gene in B-cell chronic lymphocytic leukemia cells, T cells, and hematopoietic cell lines: cell-type-independent-induction of CD23, CD21, and ICAM-1. Leukemia 7, 104–112 (1993).
pubmed: 8093369
Kis, L. L., Takahara, M., Nagy, N., Klein, G. & Klein, E. IL-10 can induce the expression of EBV-encoded latent membrane protein-1 (LMP-1) in the absence of EBNA-2 in B lymphocytes and in Burkitt lymphoma- and NK lymphoma-derived cell lines. Blood 107, 2928–2935 (2006).
pubmed: 16332968
Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR–Cas9. Nat. Biotechnol. 34, 184–191 (2016).
pubmed: 26780180 pmcid: 4744125
Bostick, M. et al. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317, 1760–1764 (2007).
pubmed: 17673620
Sharif, J. et al. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 450, 908–912 (2007).
pubmed: 17994007
Avvakumov, G. V. et al. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature 455, 822–825 (2008).
pubmed: 18772889
Bashtrykov, P., Jankevicius, G., Jurkowska, R. Z., Ragozin, S. & Jeltsch, A. The UHRF1 protein stimulates the activity and specificity of the maintenance DNA methyltransferase DNMT1 by an allosteric mechanism. J. Biol. Chem. 289, 4106–4115 (2014).
pubmed: 24368767
Chen, C. et al. Uhrf1 regulates germinal center B cell expansion and affinity maturation to control viral infection. J. Exp. Med. 215, 1437–1448 (2018).
pubmed: 29618490 pmcid: 5940267
Shaknovich, R. et al. DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation. Blood 118, 3559–3569 (2011).
pubmed: 21828137 pmcid: 3186332
Wang, L. W., Jiang, S. & Gewurz, B. E. Epstein–Barr virus LMP1-mediated oncogenicity. J. Virol. 91, e01718-16 (2017).
pubmed: 28835489 pmcid: 5640852
Kieser, A. & Sterz, K. R. The latent membrane protein 1 (LMP1). Curr. Top. Microbiol. Immunol. 391, 119–149 (2015).
pubmed: 26428373
Wang, C. et al. RNA sequencing analyses of gene expression during Epstein–Barr virus infection of primary B lymphocytes. J. Virol. 93, e00226-19 (2019).
pubmed: 31019051 pmcid: 6580941
Price, A. M. et al. Analysis of Epstein–Barr virus-regulated host gene expression changes through primary B-cell outgrowth reveals delayed kinetics of latent membrane protein 1-mediated NF-κB activation. J. Virol. 86, 11096–11106 (2012).
pubmed: 22855490 pmcid: 3457162
Minamitani, T. et al. Mouse model of Epstein–Barr virus LMP1- and LMP2A-driven germinal center B-cell lymphoproliferative disease. Proc. Natl Acad. Sci. USA 114, 4751–4756 (2017).
pubmed: 28351978 pmcid: 5422827
Cohen, J. I., Wang, F., Mannick, J. & Kieff, E. Epstein–Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. Proc. Natl Acad. Sci. USA 86, 9558–9562 (1989).
pubmed: 2556717 pmcid: 298536
Pei, Y., Banerjee, S., Jha, H. C., Sun, Z. & Robertson, E. S. An essential EBV latent antigen 3C binds Bcl6 for targeted degradation and cell proliferation. PLoS Pathog. 13, e1006500 (2017).
pubmed: 28738086 pmcid: 5524291
Vaughan, R. M. et al. Chromatin structure and its chemical modifications regulate the ubiquitin ligase substrate selectivity of UHRF1. Proc. Natl Acad. Sci. USA 115, 8775–8780 (2018).
pubmed: 30104358 pmcid: 6126761
Maenohara, S. et al. Role of UHRF1 in de novo DNA methylation in oocytes and maintenance methylation in preimplantation embryos. PLoS Genet. 13, e1007042 (2017).
pubmed: 28976982 pmcid: 5643148
Bronner, C., Alhosin, M., Hamiche, A. & Mousli, M. Coordinated dialogue between UHRF1 and DNMT1 to ensure faithful inheritance of methylated DNA patterns. Genes (Basel) 10, 65 (2019).
Cheng, J. et al. Structural insight into coordinated recognition of trimethylated histone H3 lysine 9 (H3K9me3) by the plant homeodomain (PHD) and tandem tudor domain (TTD) of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) protein. J. Biol. Chem. 288, 1329–1339 (2013).
pubmed: 23161542
Arita, K. et al. Recognition of modification status on a histone H3 tail by linked histone reader modules of the epigenetic regulator UHRF1. Proc. Natl Acad. Sci. USA 109, 12950–12955 (2012).
pubmed: 22837395 pmcid: 3420164
Harrison, J. S. et al. Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1. eLife 5, e17101 (2016).
pubmed: 27595565 pmcid: 5012860
Robertson, K. D. et al. CpG methylation of the major Epstein–Barr virus latency promoter in Burkitt’s lymphoma and Hodgkin’s disease. Blood 88, 3129–3136 (1996).
pubmed: 8874213
Kretzmer, H. et al. DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control. Nat. Genet. 47, 1316–1325 (2015).
pubmed: 26437030 pmcid: 5444523
Bhende, P. M., Seaman, W. T., Delecluse, H.-J. & Kenney, S. C. The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome. Nat. Genet. 36, 1099–1104 (2004).
pubmed: 15361873
Bergbauer, M. et al. CpG-methylation regulates a class of Epstein–Barr virus promoters. PLoS Pathog. 6, e1001114 (2010).
pubmed: 20886097 pmcid: 2944802
Smits, A. H. et al. Biological plasticity rescues target activity in CRISPR knock outs. Nat. Methods 16, 1087–1093 (2019).
pubmed: 31659326
Giffin, L. & Damania, B. KSHV: pathways to tumorigenesis and persistent infection. Adv. Virus Res. 88, 111–159 (2014).
pubmed: 24373311 pmcid: 4104069
Lurain, K. et al. Viral, immunologic, and clinical features of primary effusion lymphoma. Blood 133, 1753–1761 (2019).
pubmed: 30782610 pmcid: 6473499
Anastasiadou, E. et al. Epigenetic mechanisms do not control viral latency III in primary effusion lymphoma cells infected with a recombinant Epstein–Barr virus. Leukemia 19, 1854–1856 (2005).
pubmed: 16079894
Goll, M. G. & Bestor, T. H. Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem. 74, 481–514 (2005).
pubmed: 15952895
Barwick, B. G. et al. B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation. Nat. Commun. 9, 1900 (2018).
pubmed: 29765016 pmcid: 5953949
Lai, A. Y. et al. DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation. Genome Res. 23, 2030–2041 (2013).
pubmed: 24013550 pmcid: 3847773
Leonard, S. et al. Epigenetic and transcriptional changes which follow Epstein–Barr virus infection of germinal center B cells and their relevance to the pathogenesis of Hodgkin’s lymphoma. J. Virol. 85, 9568–9577 (2011).
pubmed: 21752916 pmcid: 3165764
Kelly, G., Bell, A. & Rickinson, A. Epstein–Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2. Nat. Med. 8, 1098–1104 (2002).
pubmed: 12219084
Allday, M. J. EBV finds a polycomb-mediated, epigenetic solution to the problem of oncogenic stress responses triggered by infection. Front. Genet. 4, 212 (2013).
pubmed: 24167519 pmcid: 3807040
Arvey, A. et al. An atlas of the Epstein–Barr virus transcriptome and epigenome reveals host-virus regulatory interactions. Cell Host Microbe 12, 233–245 (2012).
pubmed: 22901543 pmcid: 3424516
Sterlin, D. et al. Genetic, cellular and clinical features of ICF syndrome: a French national survey. J. Clin. Immunol. 36, 149–159 (2016).
pubmed: 26851945
Salamon, D. et al. Protein-DNA binding and CpG methylation at nucleotide resolution of latency-associated promoters Qp, Cp, and LMP1p of Epstein–Barr virus. J. Virol. 75, 2584–2596 (2001).
pubmed: 11222681 pmcid: 115881
Simon, J. A. & Kingston, R. E. Occupying chromatin: polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put. Mol. Cell 49, 808–824 (2013).
pubmed: 23473600 pmcid: 3628831
Taylor, G. S., Long, H. M., Brooks, J. M., Rickinson, A. B. & Hislop, A. D. The immunology of Epstein–Barr virus-induced disease. Annu. Rev. Immunol. 33, 787–821 (2015).
pubmed: 25706097
Ahmed, M. et al. TCR-mimic bispecific antibodies targeting LMP2A show potent activity against EBV malignancies. JCI Insight 3, e97805 (2018).
pmcid: 5916246
Ma, Y. et al. CRISPR/Cas9 screens reveal Epstein–Barr virus-transformed B cell host dependency factors. Cell Host Microbe 21, 580–591 (2017).
pubmed: 28494239 pmcid: 8938989
Lu, F. et al. Coordinate regulation of TET2 and EBNA2 controls the DNA methylation state of latent Epstein–Barr virus. J. Virol. 91, e00804-17 (2017).
pubmed: 28794029 pmcid: 5625499
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
pubmed: 23104886
Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
pubmed: 24227677
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281 pmcid: 4302049
Chen, E. Y. et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 14, 128 (2013).
pubmed: 23586463 pmcid: 3637064

Auteurs

Rui Guo (R)

Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Yuchen Zhang (Y)

Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Sun Yat-sen University Cancer Center, Guangzhou, China.

Mingxiang Teng (M)

Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
ORCID: 0000-0002-8536-8941

Chang Jiang (C)

Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Molly Schineller (M)

Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Bo Zhao (B)

Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
ORCID: 0000-0002-8612-5597

John G Doench (JG)

Broad Institute of Harvard and MIT, Cambridge, MA, USA.
ORCID: 0000-0002-3707-9889

Richard J O'Reilly (RJ)

Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Ethel Cesarman (E)

Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
ORCID: 0000-0003-3303-6299

Lisa Giulino-Roth (L)

Weill Cornell Medical College, New York, NY, USA.

Benjamin E Gewurz (BE)

Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. bgewurz@bwh.harvard.edu.
Department of Microbiology, Harvard Medical School, Boston, MA, USA. bgewurz@bwh.harvard.edu.
Broad Institute of Harvard and MIT, Cambridge, MA, USA. bgewurz@bwh.harvard.edu.
ORCID: 0000-0002-3965-3418

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes viraux › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes B › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Lymphome malin non hodgkinien › Lymphome B › Lymphome de Burkitt › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Protéines liant les séquences stimulatrices de type CCAAT › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Systèmes CRISPR-Cas › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines liant le poly-adp-ribose › DNA (Cytosine-5-)-methyltransferase 1 › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › DNA modification methylases › DNA-Cytosine Methylases › DNA (cytosine-5-)-methyltransferase › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes viraux › Antigènes nucléaires du virus d'Epstein-Barr › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes viraux › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome microbien › Génome viral › Gènes viraux › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome microbien › Génome viral › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Virus › Virus oncogènes › Virus tumoraux à ADN › Gammaherpesvirinae › Lymphocryptovirus › Herpèsvirus humain de type 4 › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › DNA methylation enzymes and PRC1 restrict...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › DNA methylation enzymes and PRC1 restrict...