Glucocorticoids locally disrupt an array of positioned nucleosomes on the rat tyrosine aminotransferase promoter in hepatoma cells.
Transcriptional activation by steroid hormones is often associated with the appearance of a DNase I hypersensitive site resulting from a local alteration of the nucleoprotein structure of the promoter. For the mouse mammary tumor virus long terminal repeat, a viral promoter under glucocorticoid control, a model has been proposed: the appearance of the hormonodependent DNase I hypersensitive site reflects the displacement of a single precisely positioned nucleosome associated with the glucocorticoid responsive elements. To determine if such a mechanism is of general relevance in transcriptional activation by steroid hormones, we have investigated the nucleosomal organization of the rat tyrosine aminotransferase promoter over a 1-kilobase region that contains the glucocorticoid regulatory target. This region displays a hormonodependent DNase I hypersensitive site. In the absence of hormone, micrococcal nuclease digestion of nuclei demonstrates the presence of positioned nucleosomes, with cutting sites centered around positions -3080, -2900, -2700, -2800, -2255, and -2040. Treatment of the cells with dexamethasone induces a disruption of the chromatin structure over a relatively short stretch of DNA (approximately positions -2400 to -2650) that overlaps two nucleosomes. These observations suggest a strong similarity in the role of chromatin structure in glucocorticoid-dependent transcriptional activation of mouse mammary tumor virus and tyrosine aminotransferase promoters.
Carr
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KD
Unité de Recherches sur les Communications Hormonales, Institut National de la Santé et de la Recherche Médicale U-33, Hôpital du Kremlin Bicêtre, France.
Richard-Foy
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H
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003850:Deoxyribonuclease I; D003907:Dexamethasone / Q000494:pharmacology*; D005796:Genes / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics; D008836:Micrococcal Nuclease; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism*; D009710:Nucleotide Mapping; D011401:Promoter Regions, Genetic; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D014158:Transcription, Genetic / Q000187:drug effects; D014444:Tyrosine Transaminase / Q000235:genetics*
D009707:Nucleosomes; D003907:Dexamethasone; D014444:Tyrosine Transaminase; D003850:Deoxyribonuclease I; D008836:Micrococcal Nuclease