Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Amino Acid Motifs
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Binding Sites
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Cell Line, Tumor
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Chromatin Assembly and Disassembly
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Co-Repressor Proteins
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation / physiology
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HeLa Cells
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Histone Deacetylases / metabolism*
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Histone Demethylases
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Histones / metabolism
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Humans
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Methylation
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Models, Genetic
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Oxidoreductases, N-Demethylating / metabolism*
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Promoter Regions, Genetic
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Protein Interaction Mapping
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Recombinant Proteins / analysis
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Sequence Alignment
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Small Ubiquitin-Related Modifier Proteins / metabolism*
Substances
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Co-Repressor Proteins
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DNA-Binding Proteins
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Histones
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Nerve Tissue Proteins
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RCOR1 protein, human
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Recombinant Proteins
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Repressor Proteins
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SUMO2 protein, human
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Small Ubiquitin-Related Modifier Proteins
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Histone Demethylases
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KDM1A protein, human
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Oxidoreductases, N-Demethylating
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Histone Deacetylases