N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso.

The identification and characterization of molecular mechanisms utilized by cells to mediate transcriptional repression at methylated loci are fundamental to understanding the biological consequences of DNA methylation. Here we demonstrate that Kaiso, a methyl CpG binding protein belonging to the BTB/POZ family of transcription factors, is a component of the ...
human N-CoR complex. In vitro, the Kaiso/N-CoR complex binds specific CpG-rich sequences in a methylation-dependent manner. In vivo, Kaiso targets the N-CoR complex to the MTA2 gene promoter in a methylation-dependent manner. Importantly, we demonstrate that Kaiso is required for transcriptional repression of the methylated MTA2 locus. Furthermore, this repression also requires a functional N-CoR deacetylase complex, which brings about histone hypoacetylation and methylation of H3 lysine 9 to the MTA2 locus. Thus, our data demonstrate a critical role for a methyl CpG binding protein in mediating DNA methylation-dependent repression and reveal the mechanism by which it represses transcription.
Mesh Terms:
Animals, Carrier Proteins, CpG Islands, DNA Methylation, DNA-Binding Proteins, DNA-Cytosine Methylases, Eukaryotic Cells, Genes, Regulator, Hela Cells, Histone Deacetylases, Histones, Humans, Lysine, Nuclear Proteins, Nuclear Receptor Co-Repressor 1, Promoter Regions, Genetic, Repressor Proteins, Transcription Factors
Mol. Cell
Date: Sep. 01, 2003
Download Curated Data For This Publication
8697
Switch View:
  • Interactions 15