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Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly.

In mammals, heterochromatin is characterized by DNA methylation at CpG dinucleotides and methylation at lysine 9 of histone H3. It is currently unclear whether there is a coordinated transmission of these two epigenetic modifications through DNA replication. Here we show that the methyl-CpG binding protein MBD1 forms a stable complex with histone H3-K9 methylase SETDB1. Moreover, during DNA replication, MBD1 recruits SETDB1 to the large subunit of chromatin assembly factor CAF-1 to form an S phase-specific CAF-1/MBD1/SETDB1 complex that facilitates methylation of H3-K9 during replication-coupled chromatin assembly. In the absence of MBD1, H3-K9 methylation is lost at multiple genomic loci and results in activation of p53BP2 gene, normally repressed by MBD1 in HeLa cells. Our data suggest a model in which H3-K9 methylation by SETDB1 is dependent on MBD1 and is heritably maintained through DNA replication to support the formation of stable heterochromatin at methylated DNA.

Pubmed ID: 15327775


  • Sarraf SA
  • Stancheva I


Molecular cell

Publication Data

August 27, 2004

Associated Grants


Mesh Terms

  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Chromatin Assembly and Disassembly
  • CpG Islands
  • DNA Replication
  • DNA-Binding Proteins
  • Gene Silencing
  • HeLa Cells
  • Histones
  • Humans
  • Lysine
  • Macromolecular Substances
  • Methylation
  • Models, Biological
  • Promoter Regions, Genetic
  • Protein Methyltransferases
  • Proteins
  • RNA, Small Interfering
  • S Phase
  • Transcription Factors
  • Two-Hybrid System Techniques