title: Retinoid-induced chromatin structure alterations in the retinoic acid receptor beta2 promoter.
abstract: Transcription of the retinoic acid receptor beta2 (RARbeta2) gene is induced by retinoic acid (RA) in mouse P19 embryonal carcinoma (EC) cells. Here we studied RA-induced chromatin structure alterations in the endogenous RARbeta2 promoter and in an integrated, multicopy RARbeta2 promoter in EC cells. RA markedly increased restriction site accessibility within the promoter, including a site near the RA responsive element (RARE) to which the nuclear receptor retinoid X receptor (RXR)-RAR heterodimer binds. These changes coincided with RA-induced alterations in the DNase I hypersensitivity pattern in and around the promoter. These changes became undetectable upon removal of RA, which coincided with the extinction of transcription. Analyses with receptor-selective ligands and an antagonist showed that increase in restriction site accessibility correlates with transcriptional activation, which parallels the RA-induced in vivo footprint of the promoter. Despite these changes, the micrococcal nuclease digestion profile of this promoter was not altered by RA. These results indicate that concurrent with the binding of the RXR-RAR heterodimer to the RARE, the local chromatin structure undergoes dynamic, reversible changes in and around the promoter without globally affecting the nucleosomal organization.
authors.affiliation: Laboratory of Molecular Growth and Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bhattacharyya
authors.forename: A
authors.initials: A
authors.lastname: Dey
authors.forename: S
authors.initials: S
authors.lastname: Minucci
authors.forename: A
authors.initials: A
authors.lastname: Zimmer
authors.forename: S
authors.initials: S
authors.lastname: John
authors.forename: G
authors.initials: G
authors.lastname: Hager
authors.forename: K
authors.initials: K
authors.lastname: Ozato
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D002843:Chromatin / Q000187:drug effects*; D018983:DNA Footprinting; D015972:Gene Expression Regulation, Neoplastic; D008024:Ligands; D051379:Mice; D008836:Micrococcal Nuclease / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000235:genetics*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D001565:Benzoates; D002839:Chromans; D002843:Chromatin; D008024:Ligands; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; C084904:Ro 41-5253; D014212:Tretinoin; D008836:Micrococcal Nuclease