Modification of deoxyribonucleic acid-thyroid hormone receptor interaction by histones.
The effects of histones on receptor-DNA interaction were examined using an in vitro DNA-cellulose-binding assay of [125I]T3 receptor. H1 histones bound to DNA-cellulose strongly inhibited binding of receptor to DNA-cellulose. DNA-cellulose column chromatography showed that 80% of T3-binding activity attached to DNA-cellulose could be eluted using 1 mg H1 histone/ml at low ionic strength. The potent inhibitory activity of H1 histones on receptor-DNA binding was reversed by removal of H1 histones from DNA-cellulose or by removal of H1 histones from receptor. The interaction was specific for the DNA-binding activity of receptor, since H1 histones inhibit neither T3-binding activity nor core histone-binding activity of receptor. In contrast, low concentrations of core histones enhanced binding of T3 receptor to DNA-cellulose. This effect was also seen when DNA-cellulose was treated with core histones and then deprived of free core histones. The enhancement was reversed by removal of core histones bound to DNA-cellulose. A tryptic fragment of the receptor, which lost DNA-binding activity but retained hormone and core histone-binding activities, was capable of binding to DNA-cellulose in the presence of core histones. These data suggest that enhanced binding of receptor to DNA-cellulose by core histones is mediated through the core histone-binding activity of receptor. A heat-labile protein factor in nuclear extracts (possibly receptor itself) also enhanced receptor binding to DNA-cellulose. Our data suggest important roles of histones in the organization of nuclear thyroid hormone receptors in chromatin. Since H1 histone participates in condensation of chromatin and is enriched in transcriptionally inactive chromatin, inhibition of DNA-binding activity of receptor by H1 histone bound to DNA could explain the preferential binding of nuclear thyroid hormone receptor to transcriptionally active chromatin.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000031:analogs & derivatives / Q000378:metabolism*; D006657:Histones / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000648:ultrastructure; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism; D014357:Trypsin
C033190:DNA-cellulose; D006657:Histones; D010446:Peptide Fragments; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D002482:Cellulose; D004247:DNA; D014357:Trypsin