Co-activators and co-repressors in the integration of transcriptional responses.
The nuclear hormone receptors are DNA binding transcription factors that are regulated by binding of ligands, switching them from an inactive or repressive state to gene-activating functions. Recent evidence supports the hypothesis that many nuclear receptors switch, in a ligand-dependent manner, between binding of a multicomponent co-repressor complex containing histone deacetyltransferase activity, and binding of a co-activator complex containing factors with histone acetyltransferase activity that are further regulated by diverse signal transduction pathways. The identification of these limiting co-repressor and co-activator complexes and their specific interaction motifs, in concert with solution of the structures of the receptor ligand-binding domain in apo (empty) and ligand bound forms, indicates a common molecular mechanism by which these factors activate and repress gene transcription.
Torchia
J
J
Howard Hughes Medical Institute, University of California San Diego 92093, USA. jtorchia@julian.uwo.ca
Glass
C
C
Rosenfeld
M G
MG
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases