CoREST1

CoREST1, also known as REST corepressor 1, is a transcriptional corepressor protein encoded by the RCOR1 gene in humans. It is a core component of the REST/CoREST/LSD1 repression complex, which functions to repress neuronal gene expression in non-neuronal cells and during neural development.

Mechanistically, CoREST1 forms a multiprotein complex with REST (the repressor of neuron-specific genes) and the histone-modifying enzymes LSD1/KDM1A and HDAC1/2. Through this complex, CoREST1 contributes to demethylation of histone H3 on lysines 4 (H3K4me1/2) and histone deacetylation, creating a repressive chromatin environment at target promoters that often contain RE1/NRSE elements. REST recruits CoREST1 to these sites to execute transcriptional silencing.

CoREST1 is part of a small RCOR gene family that includes RCOR2 (CoREST2) and RCOR3 (CoREST3). These proteins share functional similarities and can form alternative repressor complexes, with expression patterns that vary by tissue and developmental stage, contributing to context-dependent regulation of gene expression.

Biological roles of CoREST1 encompass neural development, neuronal differentiation, and the maintenance of neuronal identity. By shaping chromatin states at specific gene networks, CoREST1 participates in epigenetic regulation across various cell types and developmental contexts. Disruption of CoREST1 function or its interaction with REST can alter gene expression programs and has been discussed in relation to neurodevelopmental processes and cancer biology.

Clinical relevance and research interest: CoREST1 is a focal point in studies of epigenetic regulation, with interest in cancer biology and neurodevelopmental disorders. Pharmacological strategies that perturb LSD1 and REST-CoREST interactions can influence neuronal gene expression in model systems, highlighting the functional importance of this corepressor axis.