Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element.
A derivative of mouse mammary tumor virus (MTV) DNA, LTL, was constructed in vitro and introduced into the genome of mouse L cells. Transcription of LTL was stimulated by dexamethasone, a glucocorticoid hormone. Two features of LTL chromatin structure are altered upon hormone treatment. First, "moderate" DNAase I sensitivity of the entire LTL element increases following addition of dexamethasone; this alteration persists after hormone withdrawal, when LTL transcription is shut off. Second, a discrete DNAase I-hypersensitive region is induced with a time course that closely parallels the rate of increasing transcription from the MTV promoter; this structure disappears upon hormone removal. The induced hypersensitive region coincides with a segment of the MTV long terminal repeat sequence that specifically binds purified glucocorticoid receptor in vitro and functions as a hormone-dependent enhancer element in vivo. We suggest that specific glucocorticoid receptor-DNA interactions may alter the configuration of DNA or chromatin in the vicinity of the binding sites, thereby creating an active transcriptional enhancer.
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002843:Chromatin / Q000502:physiology*; D004262:DNA Restriction Enzymes; D003907:Dexamethasone / Q000494:pharmacology*; D005796:Genes / Q000187:drug effects*; D005814:Genes, Viral / Q000187:drug effects*; D007739:L Cells / Q000187:drug effects / Q000201:enzymology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D013937:Thymidine Kinase / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D002843:Chromatin; D003907:Dexamethasone; D013937:Thymidine Kinase; D004262:DNA Restriction Enzymes