Alterations in chromatin structure associated with glucocorticoid-induced expression of endogenous mouse mammary tumor virus genes.
Alterations in the chromatin structure of endogenous mouse mammary tumor virus genes accompany glucocorticoid induction of viral RNA synthesis in the C57BL/6 T lymphoma cell line T1M1. These alterations are defined by the appearance of sites of DNase I hypersensitivity within proviral DNA in isolated nuclei, as well as by changes in the moderate nuclease sensitivity of entire proviral transcription units. Induced hypersensitive sites, termed type I, appear with a time course comparable to that required for induction of the rate of viral RNA synthesis and are maintained only in the continuous presence of hormone. Two such sites map to analogous positions in the 5' and 3' long terminal repeats of proviral DNA within, or very near, sequences that have been shown to comprise positions of specific binding of the glucocorticoid receptor in vitro and that are required for hormone-inducible transcription in vivo. A third type I site maps to another position of in vitro receptor binding near the 3' long terminal repeat. Some sites of DNase I hypersensitivity, termed type II, appear not to be markedly hormone dependent; two such sites are present in corresponding positions in each long terminal repeat. Comparison of the moderate DNase I sensitivity of mouse mammary tumor virus proviral DNA suggests that the three different endogenous units in T1M1 cells can be maintained in distinct chromatin conformations that are determined by factors related to the site of provirus insertion. It seems possible that altered chromatin conformations may reflect, or actually encode, important mechanistic features of these hormone-responsive genes.
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D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure; D002843:Chromatin / Q000502:physiology / Q000648:ultrastructure*; D003850:Deoxyribonuclease I; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005814:Genes, Viral; D008223:Lymphoma; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009857:Oncogenes; D014158:Transcription, Genetic
D002843:Chromatin; D003907:Dexamethasone; D003850:Deoxyribonuclease I