CoREST3

CoREST3, also known as RCOR3, is a member of the CoREST family of transcriptional corepressors that cooperate with the REST (RE1-silencing transcription factor) to regulate gene expression. It is encoded by the RCOR3 gene and is one of three RCOR family members, alongside RCOR1 (CoREST1) and RCOR2 (CoREST2). The protein contains domains characteristic of CoREST proteins, including a SANT-like domain implicated in chromatin remodeling.

In transcriptional regulation, CoREST3 participates in a multiprotein complex with REST and chromatin-modifying enzymes such as histone deacetylases HDAC1 and HDAC2, and the histone demethylase LSD1 (KDM1A). Through this complex, CoREST3 contributes to histone deacetylation and H3K4 demethylation at REST target loci, promoting a repressive chromatin state and silencing of neuronal genes in non-neuronal contexts. The REST/CoREST3 complex is also involved in regulation during neural development and differentiation.

Expression of RCOR3 has been detected in multiple tissues, with detection in neural tissue reported and distribution that can vary between studies. CoREST3 is thought to function with partial redundancy alongside CoREST1 and CoREST2, while potentially possessing distinct gene targets and context-dependent roles. Current research focuses on identifying the specific gene targets of RCOR3-containing complexes and elucidating their roles in development, neural function, and disease. As part of the REST/CoREST axis, RCOR3 contributes to broader chromatin-based mechanisms of transcriptional regulation.