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.
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
Mol. Cell
Date: Aug. 27, 2004
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