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PMID: 11350943 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription.

The EMBO journal ·Vol. 20 ·No. 10 ·2001-05-15 ·Pages 2536-44

Fuks F, Burgers WA, Godin N, Kasai M, Kouzarides T

Abstract

The Dnmt3a DNA methyltransferase is essential for mammalian development and is responsible for the generation of genomic methylation patterns, which lead to transcriptional silencing. Here, we show that Dnmt3a associates with RP58, a DNA-binding transcriptional repressor protein found at transcriptionally silent heterochromatin. Dnmt3a acts as a co-repressor for RP58 in a manner that does not require its de novo methyltransferase activity. Like other characterized co-repressors, Dnmt3a associates with the histone deacetylase HDAC1 using its ATRX-homology domain. This domain of Dnmt3a represents an independent transcriptional repressor domain whose silencing functions require HDAC activity. These results identify Dnmt3a as a co-repressor protein carrying deacetylase activity and show that Dnmt3a can be targeted to specific regulatory foci via its association with DNA-binding transcription factors.

MeSH Terms
Binding Sites Cell Line, Transformed DNA (Cytosine-5-)-Methyltransferases/genetics,metabolism,physiology DNA Helicases DNA Methylation DNA Methyltransferase 3A DNA-Binding Proteins/metabolism Gene Silencing Histone Deacetylase 1 Histone Deacetylases/metabolism Humans Nuclear Proteins Repressor Proteins/genetics,metabolism Saccharomyces cerevisiae Transcription Factors/genetics,metabolism Transcription, Genetic Tumor Cells, Cultured Two-Hybrid System Techniques X-linked Nuclear Protein
Chemicals
DNA-Binding Proteins DNMT3A protein, human Nuclear Proteins Repressor Proteins Transcription Factors ZBTB18 protein, human DNA (Cytosine-5-)-Methyltransferases DNA Methyltransferase 3A HDAC1 protein, human Histone Deacetylase 1 Histone Deacetylases DNA Helicases ATRX protein, human X-linked Nuclear Protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Fuks F
Wellcome/CRC Institute and Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QR, UK.
Burgers W A
Godin N
Kasai M
Kouzarides T
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.10.2536
Published
2001-05-15
Pages
2536-44
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125250
Subset
IM
Corrections
CommentIn
PMID: 33714886
External Links
PubMed source DOI: 10.1093/emboj/20.10.2536 PMC Full Text View journal details
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