RESTCoREST3

RESTCoREST3 is a term used in the field of epigenetic regulation to describe a proposed variant of the REST–CoREST transcriptional repressor complex. REST (RE1-silencing transcription factor) and the CoREST family of corepressors recruit histone-modifying enzymes to silence neuronal genes in non-neuronal cells and to regulate neuronal differentiation. In canonical models, REST associates with CoREST proteins and histone demethylases and deacetylases to modulate chromatin. RESTCoREST3 denotes a putative third component or a distinct assembly that can accompany REST and CoREST in certain cellular contexts, potentially altering the pattern of chromatin modification and target gene selection.

The exact composition of RESTCoREST3 is not settled. Proposals suggest the involvement of an additional corepressor or chromatin-modifying enzyme that can change the balance of histone marks at REST-target sites, leading to differences in repression strength or developmental timing. Some studies have reported detection of a higher-order complex in neural progenitor cells, while others have failed to reproduce stable RESTCoREST3 associations, pointing to context-dependent or transient interactions.

Current understanding places RESTCoREST3 as an area of active investigation rather than an established, universally accepted complex. If confirmed, it could refine models of transcriptional repression during neurodevelopment and may have implications for disorders involving REST signaling. Ongoing research aims to define its components, prevalence, and functional impact.