Glucocorticoids Locally Disrupt an Array of Positioned Nucleosomes on the Rat Tyrosine Aminotransferase Promoter in Hepatoma Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 1990-12, Vol.87 (23), p.9300-9304
• Main Authors: Carr, Kimberly D., Richard-Foy, Helene
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cell Line; Cell lines; Chromatin; Chromatin. Chromosome; Deoxyribonuclease I; Dexamethasone - pharmacology; DNA; DNA probes; Fundamental and applied biological sciences. Psychology; Genes - drug effects; Glucocorticoids; Hormones; Hypersensitivity; Liver Neoplasms, Experimental - enzymology; Liver Neoplasms, Experimental - genetics; Micrococcal Nuclease; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Nucleosomes; Nucleosomes - drug effects; Nucleosomes - metabolism; Nucleotide Mapping; Promoter regions; Promoter Regions, Genetic; Rats; Regulatory Sequences, Nucleic Acid; Restriction Mapping; Transcription, Genetic - drug effects; Transcriptional activation; Tyrosine Transaminase - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.23.9300

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, -2480, -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.