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

The Dnmt3a DNA methyltransferase is essential for mammalian development and is responsible for the generation of genomic methylation patterns, which l ead to transcriptional silencing. Here, we show that Dnmt3a associates with RP58, a DNA-binding transcriptional repressor protein found at transcripti onally silent heterochromatin. Dnmt3a acts as a corepressor for RP58 in a m anner that does not require its de novo methyltransferase activity. Like ot her characterized co-repressors, Dnmt3a associates with the histone deacety lase 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 prot ein carrying deacetylase activity and show that Dnmt3a can be targeted to s pecific regulatory foci via its association with DNA-binding transcription factors.