title: Complex role of histone H1 in transactivation of MMTV promoter chromatin by progesterone receptor.
abstract: Transcription from the mouse mammary tumor virus (MMTV) promoter can be induced by glucocorticoids or progestins. The corresponding receptors bind to a cluster of hormone responsive elements (HREs) and activate the promoter by synergistic interactions with ubiquitous transcription factors, in particular nuclear factor 1 (NF1). Synergism between hormone receptors and NF1 depends on the precise positioning of the promoter sequences on the surface of a histone octamer in chromatin, but how linker histones participate in the process is unclear. Asymmetric binding of histone H1 to chromatin organized MMTV promoter sequences compacts the nucleosomal structure and leads to repression of basal transcription and to reduced binding of NF1. In contrast, H1 containing MMTV chromatin binds PR with higher affinity and is transcribed more efficiently in the presence of PR and NF1 than chromatin free of linker histone. Thus histone H1 represses hormone independent transcription and enhances the synergism between PR and NF1 resulting in tighter hormonal regulation. This positive effect of H1 is likely due to a better defined nucleosome positioning over the MMTV promoter. Upon binding of PR to the promoter chromatin a hitherto unidentified kinase is recruited or activated that phosphorylates H1. This is not sufficient for transcriptional activation but is likely a requisite for the action of ATP-dependent chromatin remodelling complexes. Following remodelling and in the presence of NF1, which maintains the open nucleosome conformation, additional PR molecules bind, transactivation takes place and H1 is displaced from the promoter during transcription initiation. Therefore, H1 plays a key role during the initial hormonal activation of the MMTV promoter in native chromatin, which includes recruitment by PR of a histone H1 kinase and an ATP-dependent chromatin remodelling complex, followed by NF1 binding, increased PR binding, transcription initiation and H1 displacement.
authors.affiliation: Institut für Molekularbiologie und Tumorforschung, Philipps-Universität, Emil-Mannkopff-Str., 2, D-35037 Marburg, Germany.
authors.forename: Guillermo P
authors.initials: GP
authors.lastname: Vicent
authors.forename: Ronald
authors.initials: R
authors.lastname: Koop
authors.forename: Miguel
authors.initials: M
authors.lastname: Beato
mesh_terms: D000818:Animals; D002417:Cattle; D002843:Chromatin / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D008745:Methylation; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D011980:Receptors, Progesterone / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D011980:Receptors, Progesterone