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Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS proteins.

In mammalian cells, DNA methylation is associated with heritable and stable gene repression, mediated in part by methyl-CpG-binding domain (MBD) proteins that recruit corepressors to modify chromatin. MBD1 protein, a member of the MBD family, forms a complex with SETDB1 histone methylase to silence transcription at target promoters by methylation of lysine 9 of histone H3. How MBD1-mediated transcriptional repression is regulated is currently unknown. Here we show that MBD1 is a target for sumoylation by PIAS1 (Protein Inhibitors of Activated STAT 1) and PIAS3 E3 SUMO (small ubiquitin-like modifier)-ligases, at two conserved lysine residues within the C-terminus of MBD1. Although sumoylated MBD1 binds to methylated DNA, it does not incorporate into a complex with SETDB1 and does not efficiently repress transcription of a target gene, p53BP2, in HeLa cells. Our data suggest that transcriptional silencing by MBD1 is regulated by a PIAS-mediated conjugation of SUMO1, which antagonizes the formation of a repressive complex with SETDB1.

Pubmed ID: 17066076

Authors

  • Lyst MJ
  • Nan X
  • Stancheva I

Journal

The EMBO journal

Publication Data

November 15, 2006

Associated Grants

  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Amino Acid Sequence
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Chromatin
  • Conserved Sequence
  • DNA Methylation
  • DNA-Binding Proteins
  • Down-Regulation
  • Gene Silencing
  • HeLa Cells
  • Histones
  • Humans
  • Molecular Chaperones
  • Molecular Sequence Data
  • Protein Binding
  • Protein Inhibitors of Activated STAT
  • Protein Methyltransferases
  • SUMO-1 Protein
  • Sequence Homology, Amino Acid
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • Transcription, Genetic