Corepressoren

Corepressoren, or corepressors, are proteins that oppose transcription by interacting with transcription factors or nuclear receptors rather than binding DNA directly. They are components of repressive chromatin-modifying complexes that help keep gene expression in check by promoting a closed chromatin state and limiting recruitment of the transcriptional machinery.

Mechanistically, corepressors can block transcription by competing with coactivators for transcription factor interaction or by actively recruiting chromatin-modifying enzymes. These enzymes include histone deacetylases and other chromatin remodelers that remove activating marks from histones, leading to chromatin condensation and reduced RNA polymerase II activity. In many systems, ligand binding to nuclear receptors triggers the dissociation of corepressors and the recruitment of coactivators, switching transcription from repressed to activated states.

Major examples and complexes include nuclear receptor co-repressors NCoR1 and NCoR2/SMRT, which form large repressive assemblies with HDAC3 and other factors. Additional corepressors such as CtBP1/2 and the Groucho/TLE family (TLE1-4) function with diverse transcription factors to repress gene expression. These corepressors can operate in development, metabolism, and cellular differentiation by shaping the transcriptional response to signaling cues.

Physiological significance and regulation are broad. Corepressors participate in development, tissue homeostasis, and disease, with activity controlled by signaling pathways, post-translational modifications, and protein turnover. Dysregulation of corepressor function has been linked to cancer, metabolic disorders, and developmental abnormalities, making them a focus of research into transcriptional control and therapeutic targeting.