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Rountree, MR, Bachman, KE and Baylin, SB (2000) DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat. Genet. 25:269-77
DNA methylation can contribute to transcriptional silencing through several transcriptionally repressive complexes, which include methyl-CpG binding domain proteins (MBDs) and histone deacetylases (HDACs). We show here that the chief enzyme that maintains mammalian DNA methylation, DNMT1, can also establish a repressive transcription complex. The non-catalytic amino terminus of DNMT1 binds to HDAC2 and a new protein, DMAP1 (for DNMT1 associated protein), and can mediate transcriptional repression. DMAP1 has intrinsic transcription repressive activity, and binds to the transcriptional co-repressor TSG101. DMAP1 is targeted to replication foci through interaction with the far N terminus of DNMT1 throughout S phase, whereas HDAC2 joins DNMT1 and DMAP1 only during late S phase, providing a platform for how histones may become deacetylated in heterochromatin following replication. Thus, DNMT1 not only maintains DNA methylation, but also may directly target, in a heritable manner, transcriptionally repressive chromatin to the genome during DNA replication.
Amino Acid Sequence; Animals; Base Sequence; COS Cells; Cercopithecus aethiops; DNA (Cytosine-5-)-Methyltransferase/genetics; DNA (Cytosine-5-)-Methyltransferase/metabolism; DNA Replication; DNA, Complementary; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Endosomal Sorting Complexes Required for Transport; Gene Expression Regulation; Genes, Reporter; Histone Deacetylase 2; Histone Deacetylases/metabolism; Humans; Hydro-Lyases/genetics; Mice; Molecular Sequence Data; Repressor Proteins/genetics; Repressor Proteins/metabolism; S Phase; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic; Vero Cells