RCOR1

RCOR1, also known as REST corepressor 1 or CoREST-1, is a nuclear protein that functions as a transcriptional corepressor in vertebrates. It is a component of the CoREST complex, together with the histone demethylase LSD1 (KDM1A) and histone deacetylases HDAC1 and HDAC2. The complex is recruited to target genes by REST (RE1-silencing transcription factor), a sequence-specific DNA-binding repressor that controls neuronal gene expression in non-neuronal cells and during development.

Functionally, the CoREST/LSD1/HDAC complex represses transcription through epigenetic mechanisms. LSD1 demethylates histone H3 on lysines 4, 1/2, removing activating marks, while HDAC1/2 remove acetyl groups, promoting chromatin condensation. RCOR1 acts as a scaffold and regulatory subunit that stabilizes the complex and modulates its targeting and activity, influencing the repression of REST-regulated genes.

RCOR1 is predominantly nuclear and is widely expressed, with notable expression in the brain, consistent with roles in neural development and differentiation.

RCOR1 directly interacts with REST, LSD1, and HDAC1/2; it belongs to the CoREST family, with two paralogs, RCOR2 and RCOR3, that share functional similarities. The protein contains domains that mediate protein-protein interactions essential for complex assembly.

Dysregulation of REST/CoREST signaling, in which RCOR1 participates, has been linked to neurodevelopmental processes and various cancers. RCOR1 and the CoREST complex are studied as models of epigenetic gene silencing and as potential therapeutic targets in diseases with epigenetic misregulation.