NCoR

Nuclear receptor co-repressor (NCoR) refers to a family of transcriptional corepressors that participate in the negative regulation of gene expression by nuclear hormone receptors and other transcription factors. The best characterized members are NCoR1 (often simply called NCoR) and NCoR2, also known as SMRT (silencing mediator of retinoic and thyroid receptors). Both are large nuclear proteins that function as platforms for assembling repressive complexes and can shuttle between the nucleus and chromatin.

Mechanism and components: In the absence of ligand, many nuclear receptors recruit NCoR/SMRT to target gene promoters or enhancers, where they recruit histone deacetylase 3 (HDAC3) as part of a multi-protein deacetylase complex, leading to chromatin condensation and transcriptional repression. NCoR/SMRT complexes typically include additional factors such as TBL1XR1, TBLR1 and GPS2, and they interact with a range of transcription factors beyond classical nuclear receptors.

Regulation: Repression by NCoR/SMRT is dynamic and can be modulated by ligand binding, post-translational modifications, and signaling pathways that alter complex composition and occupancy. Phosphorylation, acetylation, ubiquitination and interactions with other coregulators influence stability, localization and activity.

Biological roles: NCoR1 and NCoR2 regulate development, metabolism, circadian rhythm and cell differentiation. In animal models, loss of these corepressors disrupts essential processes and can be lethal or cause metabolic abnormalities. They influence lipid and glucose metabolism in liver and adipose tissue and participate in hormone signaling networks linked to growth and differentiation.

Clinical and research relevance: Because they interface with many nuclear receptors, NCoR and SMRT are important in epigenetic regulation of gene expression and receptor signaling. They are studied in contexts ranging from development and metabolism to cancer and circadian biology.