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

Mol Cell. 2009 Apr 24;34(2):145-54. doi: 10.1016/j.molcel.2009.03.013.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amino Acid Motifs
  • Binding Sites
  • Cell Line, Tumor
  • Chromatin Assembly and Disassembly
  • Co-Repressor Proteins
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / physiology
  • HeLa Cells
  • Histone Deacetylases / metabolism*
  • Histone Demethylases
  • Histones / metabolism
  • Humans
  • Methylation
  • Models, Genetic
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oxidoreductases, N-Demethylating / metabolism*
  • Promoter Regions, Genetic
  • Protein Interaction Mapping
  • Recombinant Proteins / analysis
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Small Ubiquitin-Related Modifier Proteins / metabolism*


  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Histones
  • Nerve Tissue Proteins
  • RCOR1 protein, human
  • Recombinant Proteins
  • Repressor Proteins
  • SUMO2 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Histone Demethylases
  • KDM1A protein, human
  • Oxidoreductases, N-Demethylating
  • Histone Deacetylases