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

Nat Genet. 2000 Jul;25(3):269-77. doi: 10.1038/77023.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Chlorocebus aethiops
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / 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

Substances

  • DMAP1 protein, human
  • DNA, Complementary
  • DNA-Binding Proteins
  • Dmap1 protein, mouse
  • Endosomal Sorting Complexes Required for Transport
  • Repressor Proteins
  • Transcription Factors
  • Tsg101 protein
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human
  • Dnmt1 protein, mouse
  • Hdac2 protein, mouse
  • Histone Deacetylase 2
  • Histone Deacetylases
  • Hydro-Lyases
  • imidazoleglycerolphosphate dehydratase

Associated data

  • GENBANK/AF265228
  • GENBANK/AF265229