Thyroid hormone nuclear receptor levels are influenced by the acetylation of chromatin-associated proteins.

摘要: The thyroid hormone receptor is a chromatin-associated protein which appears to mediate the actions of hormones in mammalian cells. Unlike steroid receptors, cytoplasmic form has not been identified, and factors govern nuclear concentrations are poorly understood. Using cultured GH1 cells, rat pituitary cell line, we having previously demonstrated that reduces concentration its by mechanism involves association ligand with binding site (Samuels, H.H., Stanley, F., Shapiro, L.E. (1977) J. Biol. Chem. 252, 6052-6060). In this study, demonstrate n-butyrate other aliphatic carboxylic acids elicit reduction levels without altering total synthetic rates. contrast, level glucocorticoid altered n-butyrate. Evidence presented acid-mediated secondary inhibitory effect these compounds on deacetylases reflected as an increase acetylation nucleosome core histones. Isokinetic gradient centrifugation chromatin solubilized from nuclei micrococcal nuclease indicates exists associated high molecular weight chromatin, 12.5 S sediments slightly faster than bulk mononucleosomes, 6.5 remain low components. Exclusive represents 80% 10% resolved gradient. n-Butyrate decreases both forms same degree suggesting they generated "entity" structure. Studies reappearance after restoration "normal" acetylated state consistent model affinity for newly synthesized diminished "hyperacetylated" state.