Thyroid hormone receptor, v-erbA, and chromatin

摘要: The thyroid hormone receptor and the highly related viral oncoprotein v-erbA are found exclusively in nucleus as stable constituents of chromatin. Unlike most transcriptional regulators, binds with comparable affinity to naked nucleosomal DNA. In vitro reconstitution experiments vivo genomic footprinting have delineated chromatin structural features that facilitate association receptor. Chromatin bound generate Dnase I hypersensitive sites independent ligand. unliganded associate a corepressor complex containing NCoR, SIN3, histone deacetylase. enzymatic activity deacetylase environment essential for dominant repression transcription by both v-erbA. presence ligand, undergoes conformational change weakens interactions while facilitating recruitment coactivators such p300 PCAF possessing acetyltransferase activity. ligand-bound directs disruption events addition acetylation. Thus, make very effective use their capacity alter major component regulation process. This system provides an exceptionally useful paradigm investigating functional consequences targeted modification.