Direct binding of CoREST1 to SUMO-2/3 contributes to gene-specific repression by the LSD1/CoREST1/HDAC complex.

Posttranslational modification of transcription factors by the small ubiquitin-related modifier SUMO is associated with transcriptional repression, but the underlying mechanisms remain incompletely described. We have identified binding of the LSD1/CoREST1/HDAC corepressor complex to SUMO-2. Here we show that CoREST1 binds directly and noncovalently to SUMO-2, but not SUMO-1, and CoREST1 ...
bridges binding of the histone demethylase LSD1 to SUMO-2. Depletion of SUMO-2/3 conjugates led to transcriptional derepression, reduced occupancy of CoREST1 and LSD1, and changes in histone methylation and acetylation at some, but not all, LSD1/CoREST1/HDAC target genes. We have identified a nonconsensus SUMO-interaction motif (SIM) in CoREST1 required for SUMO-2 binding, and we show that mutation of the CoREST1 SIM disrupted SUMO-2 binding and transcriptional repression of some neuronal-specific genes in nonneuronal cells. Our results reveal that direct interactions between CoREST1 and SUMO-2 mediate SUMO-dependent changes in chromatin structure and transcription that are important for cell-type-specific gene expression.
Mesh Terms:
Acetylation, Amino Acid Motifs, Binding Sites, Cell Line, Tumor, Chromatin Assembly and Disassembly, DNA-Binding Proteins, Gene Expression Regulation, Hela Cells, Histone Deacetylases, Histone Demethylases, Histones, Humans, Methylation, Models, Genetic, Molecular Sequence Data, Nerve Tissue Proteins, Oxidoreductases, N-Demethylating, Promoter Regions, Genetic, Protein Interaction Mapping, Recombinant Proteins, Repressor Proteins, Sequence Alignment, Small Ubiquitin-Related Modifier Proteins
Mol. Cell
Date: Apr. 24, 2009
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