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.
Ouyang
Jian
J
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Shi
Yujiang
Y
Valin
Alvaro
A
Xuan
Yan
Y
Gill
Grace
G
D000107:Acetylation; D020816:Amino Acid Motifs; D001665:Binding Sites; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism*; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D011994:Recombinant Proteins / Q000032:analysis; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D009419:Nerve Tissue Proteins; C121019:RCOR1 protein, human; D011994:Recombinant Proteins; D012097:Repressor Proteins; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D056466:Histone Demethylases; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating; D006655:Histone Deacetylases