Article
- The EMBO Journal (2006) 25, 5317 - 5328
- doi:10.1038/sj.emboj.7601404
Published online: 26 October 2006
Subject Category:
Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS proteins
Matthew J Lyst, Xinsheng Nana and Irina Stancheva
- Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
Correspondence to:
Irina Stancheva, Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Mayfield Road, Edinburgh EH9 3JR, UK. Tel.: +44 131 650 7029; Fax: +44 131 650 7360; E-mail: istancheva@ed.ac.uk
aPresent address: MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
Received 21 April 2006; Accepted 5 October 2006
Abstract
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.
Keywords:
- chromatin,
- DNA methylation,
- MBD1,
- PIAS,
- SUMO
