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

摘要

Post-translational 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 co-repressor complex to SUMO-2. Here we show that CoREST1 binds directly and non-covalently 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 de-repression, 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 non-consensus 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 non-neuronal cells. Our results reveal that direct interactions between CoREST1 and SUMO-2 mediate SUMO-dependent changes in chromatin structure and transcription important for cell type-specific gene expression.