CoREST2

CoREST2 is a member of the CoREST family of transcriptional corepressors. In humans the protein is encoded by the RCOR2 gene and is a paralog of CoREST1 (RCOR1) and CoREST3 (RCOR3). CoREST2 participates in REST/NRSE-mediated transcriptional repression by forming a corepressor complex with the transcription factor REST (RE1-silencing transcription factor) and the histone demethylase LSD1 (KDM1A). Through this association, CoREST2 helps regulate chromatin structure and gene expression in neural and non-neural tissues.

The REST-LSD1-CoREST2 complex targets a set of neuronal genes containing REST binding sites (RE1/NRSE). LSD1 demethylates activating histone marks (H3K4me1/2), and the CoREST component recruits histone deacetylases, reinforcing a repressive chromatin state. CoREST2 is thought to influence the substrate specificity and activity of the LSD1/HDAC axis, and its presence can modulate repression relative to other CoREST paralogs.

Expression studies indicate RCOR2 is broadly expressed with enrichment in brain and developing tissues, and it shows distinct temporal and tissue-specific patterns compared with RCOR1 and RCOR3. Functional analyses suggest CoREST2 contributes to developmental gene regulation and may participate in differentiation programs, though exact gene targets and the degree of redundancy with other CoREST proteins remain under investigation.

In addition to REST-dependent repression, CoREST2 can participate in larger corepressor assemblies and interacts with HDAC1/2 and other chromatin-modifying enzymes, providing a scaffold for repression. The precise biochemical properties and regulatory mechanisms distinguishing CoREST2 from its paralogs are an active area of research.

RCOR2 disruptions or altered expression have been examined in the context of neurological development and disease, highlighting the potential clinical importance of CoREST2–REST complexes. Ongoing research seeks to clarify its specific targets, interactions, and role in development and pathology.