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

The EMBO journal | Nov 15, 2006

http://www.ncbi.nlm.nih.gov/pubmed/17066076

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 RIS Download

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

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Associated grants

  • Agency: Wellcome Trust, Id:

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