title: Four enzymes cooperate to displace histone H1 during the first minute of hormonal gene activation.
abstract: Gene regulation by external signals requires access of transcription factors to DNA sequences of target genes, which is limited by the compaction of DNA in chromatin. Although we have gained insight into how core histones and their modifications influence this process, the role of linker histones remains unclear. Here we show that, within the first minute of progesterone action, a complex cooperation between different enzymes acting on chromatin mediates histone H1 displacement as a requisite for gene induction and cell proliferation. First, activated progesterone receptor (PR) recruits the chromatin remodeling complexes NURF and ASCOM (ASC-2 [activating signal cointegrator-2] complex) to hormone target genes. The trimethylation of histone H3 at Lys 4 by the MLL2/MLL3 subunits of ASCOM, enhanced by the hormone-induced displacement of the H3K4 demethylase KDM5B, stabilizes NURF binding. NURF facilitates the PR-mediated recruitment of Cdk2/CyclinA, which is required for histone H1 displacement. Cooperation of ATP-dependent remodeling, histone methylation, and kinase activation, followed by H1 displacement, is a prerequisite for the subsequent displacement of histone H2A/H2B catalyzed by PCAF and BAF. Chromatin immunoprecipitation (ChIP) and sequencing (ChIP-seq) and expression arrays show that H1 displacement is required for hormone induction of most hormone target genes, some of which are involved in cell proliferation.
authors: Centre de Regulació Genòmica (CRG), Universitat Pompeu Fabra (UPF), E-08003 Barcelona, Spain.
authors: Guillermo Pablo
authors: GP
authors: Vicent
authors: A Silvina
authors: AS
authors: Nacht
authors: Jofre
authors: J
authors: Font-Mateu
authors: Giancarlo
authors: G
authors: Castellano
authors: Laura
authors: L
authors: Gaveglia
authors: Cecilia
authors: C
authors: Ballaré
authors: Miguel
authors: M
authors: Beato
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones; D006801:Humans; D047468:Immunoprecipitation; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011397:Promegestone / Q000494:pharmacology*; D034622:RNA Interference; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor; D000092468:Bromodomain Containing Proteins
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011397:Promegestone; D011980:Receptors, Progesterone; D012097:Repressor Proteins; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C452979:KMT2C protein, human; C120898:KMT2D protein, human; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins; C119611:KDM5B protein, human