DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.

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.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, COS Cells, Cercopithecus aethiops, DNA (Cytosine-5-)-Methyltransferase, DNA Replication, DNA, Complementary, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, Gene Expression Regulation, Genes, Reporter, Histone Deacetylase 2, Histone Deacetylases, Humans, Hydro-Lyases, Mice, Molecular Sequence Data, Repressor Proteins, S Phase, Transcription Factors, Transcription, Genetic, Vero Cells
Nat. Genet.
Date: Jul. 01, 2000
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