PMID- 10938123 OWN - NLM STAT- MEDLINE DCOM- 20000921 LR - 20240315 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 20 IP - 17 DP - 2000 Sep TI - Structure and dynamic properties of a glucocorticoid receptor-induced chromatin transition. PG - 6466-75 AB - Activation of the mouse mammary tumor virus (MMTV) promoter by the glucocorticoid receptor (GR) is associated with a chromatin structural transition in the B nucleosome region of the viral long terminal repeat (LTR). Recent evidence indicates that this transition extends upstream of the B nucleosome, encompassing a region larger than a single nucleosome (G. Fragoso, W. D. Pennie, S. John, and G. L. Hager, Mol. Cell. Biol. 18:3633-3644). We have reconstituted MMTV LTR DNA into a polynucleosome array using Drosophila embryo extracts. We show binding of purified GR to specific GR elements within a large, multinucleosome array and describe a GR-induced nucleoprotein transition that is dependent on ATP and a HeLa nuclear extract. Previously uncharacterized GR binding sites in the upstream C nucleosome region are involved in the extended region of chromatin remodeling. We also show that GR-dependent chromatin remodeling is a multistep process; in the absence of ATP, GR binds to multiple sites on the chromatin array and prevents restriction enzyme access to recognition sites. Upon addition of ATP, GR induces remodeling and a large increase in access to enzymes sites within the transition region. These findings suggest a dynamic model in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, and is then lost from the template. This model is consistent with the recent description of a "hit-and-run" mechanism for GR action in living cells (J. G. McNally, W. G. Muller, D. Walker, and G. L. Hager, Science 287:1262-1264, 2000). FAU - Fletcher, T M AU - Fletcher TM AD - Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. FAU - Ryu, B W AU - Ryu BW FAU - Baumann, C T AU - Baumann CT FAU - Warren, B S AU - Warren BS FAU - Fragoso, G AU - Fragoso G FAU - John, S AU - John S FAU - Hager, G L AU - Hager GL LA - eng PT - Journal Article PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Chromatin) RN - 0 (Ligands) RN - 0 (Nucleosomes) RN - 0 (Receptors, Glucocorticoid) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 3.1.21.1 (Deoxyribonuclease I) SB - IM MH - 3T3 Cells MH - Adenosine Triphosphate/metabolism MH - Animals MH - Binding Sites MH - CHO Cells MH - Cell Nucleus/metabolism MH - Chromatin/genetics/*metabolism MH - Cricetinae MH - Deoxyribonuclease I/metabolism MH - Dose-Response Relationship, Drug MH - Electrophoresis, Agar Gel MH - HeLa Cells MH - Humans MH - Hydrolysis MH - Ligands MH - Mammary Tumor Virus, Mouse/genetics MH - Mice MH - Mutagenesis, Site-Directed MH - Nucleosomes/metabolism MH - Plasmids/metabolism MH - Protein Binding MH - Receptors, Glucocorticoid/genetics/*metabolism MH - Terminal Repeat Sequences MH - Transfection PMC - PMC86121 EDAT- 2000/08/11 11:00 MHDA- 2000/09/23 11:01 PMCR- 2000/09/01 CRDT- 2000/08/11 11:00 PHST- 2000/08/11 11:00 [pubmed] PHST- 2000/09/23 11:01 [medline] PHST- 2000/08/11 11:00 [entrez] PHST- 2000/09/01 00:00 [pmc-release] AID - 0481 [pii] AID - 10.1128/MCB.20.17.6466-6475.2000 [doi] PST - ppublish SO - Mol Cell Biol. 2000 Sep;20(17):6466-75. doi: 10.1128/MCB.20.17.6466-6475.2000.