RCOR2

RCOR2, also known as CoREST2, is a human gene that encodes a nuclear transcriptional corepressor. It belongs to the CoREST family, which also includes RCOR1 (CoREST1) and RCOR3 (CoREST3). CoREST proteins function as part of the REST (RE1-silencing transcription factor) repressor complex that silences neuronal genes in non-neuronal cells and during early neural development.

RCOR2 participates in epigenetic silencing by forming complexes with REST and chromatin-modifying enzymes, notably the histone demethylase LSD1/KDM1A and histone deacetylases HDAC1 and HDAC2. Through interactions mediated by the ELM2-SANT domain, the complex removes activating histone marks such as H3K4me1/2 and reduces histone acetylation, thereby maintaining target genes in a repressed state.

Expression of RCOR2 is broad across tissues but tends to be enriched in brain tissue, with regulation during development and differentiation. Alternative splicing yields multiple RCOR2 isoforms, which may influence the composition and activity of REST-containing repressor complexes. Functionally, RCOR2 contributes to REST-mediated silencing to regulate neuronal gene expression programs, supporting neural differentiation and helping maintain cell identity in various cellular contexts.

Disruption or altered expression of CoREST family members, including RCOR2, has been studied in models of development, neurobiology, and cancer, highlighting their important role as epigenetic regulators of gene expression. RCOR2 operates as a component of the REST-CoREST-LSD1-HDAC repressor system and can partially compensate for other CoREST proteins, reflecting both redundancy and specificity in target gene silencing.