The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1

Mol Cell Biol. 2003 May;23(9):3226-36. doi: 10.1128/MCB.23.9.3226-3236.2003.


DNA promoter hypermethylation has been shown to be a functional mechanism of transcriptional repression. This epigenetic gene silencing is thought to involve the recruitment of chromatin-remodeling factors, such as histone deacetylases, to methylated DNA via a family of proteins called methyl-CpG binding proteins (MBD1 to -4). MBD1, a member of this family, exhibits transcription-repressive activity, but to this point no interacting protein partners have been identified. In this study, we demonstrate that MBD1 partners with the p150 subunit of chromatin assembly factor 1 (CAF-1), forming a multiprotein complex that also contains HP1alpha. The MBD1-CAF-1 p150 interaction requires the methyl-CpG binding domain of MBD1, and the association occurs in the C terminus of CAF-1 p150. The two proteins colocalize to regions of dense heterochromatin in mouse cells, and overexpression of the C terminus of CAF-1 p150 prevents the targeting of MBD1 in these cells without disrupting global heterochromatin structure. This interaction suggests a role for MBD1 and CAF-1 p150 in methylation-mediated transcriptional repression and the inheritance of epigenetically determined chromatin states.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding Sites
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Chromatin Assembly Factor-1
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone*
  • CpG Islands
  • DNA Methylation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Heterochromatin / genetics
  • Heterochromatin / metabolism
  • Humans
  • Macromolecular Substances
  • Mammals
  • Mice
  • Multiprotein Complexes
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription Factors


  • CBX5 protein, human
  • CHAF1B protein, human
  • CNOT8 protein, human
  • Carrier Proteins
  • Chaf1a protein, mouse
  • Chromatin Assembly Factor-1
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Heterochromatin
  • MBD1 protein, human
  • Macromolecular Substances
  • Mbd1 protein, mouse
  • Multiprotein Complexes
  • Repressor Proteins
  • Transcription Factors
  • Chromobox Protein Homolog 5