title: Histone acetylation and subcellular localization of chromosomal protein BRD4 during mouse oocyte meiosis and mitosis.
abstract: Most specific and general transcription factors (TFs) become dissociated from hypoacetylated mitotic chromosomes, which may contribute to transcriptional silencing during mitosis. Only some chromosomal proteins, such as bromodomain containing protein 4 (BRD4), have a potential to associate with mitotic chromosomes in a histone acetylation-dependent manner. It remains to be fully demonstrated whether similar displacement of nuclear factors takes place in meiotic oocytes whose chromosomes become globally deacetylated. To address this, we here examined the subcellular localization of BRD4 in conjunction with the acetylation status of histones in mouse oocytes. Immunofluorescence studies revealed that BRD4 preferentially localized to mitotic chromosomes in early embryos. In contrast, not only endogenous BRD4 but also exogenous BRD4 overexpressed by mRNA microinjection were displaced from meiotic chromosomes whose histones H3 and H4 were deacetylated. Treatment with trichostatin A (TSA), an inhibitor of histone deacetylases, induced histone hyperacetylation of meiotic chromosomes from which endogenous BRD4, however, remained dissociated. Finally, meiotic chromosomal localization of BRD4 could be achieved by BRD4 overexpression together with TSA-induced histone hyperacetylation. These results indicate that, unlike mitosis, histone acetylation is necessary but not sufficient for chromosomal localization of BRD4 during meiosis, suggesting that meiotic oocytes may have additional mechanism(s) for displacement of chromosomal proteins and TFs.
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagashima
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Maruyama
authors.forename: Masataka
authors.initials: M
authors.lastname: Furuya
authors.forename: Takashi
authors.initials: T
authors.lastname: Kajitani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchida
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Masuda
authors.forename: Masanori
authors.initials: M
authors.lastname: Ono
authors.forename: Toru
authors.initials: T
authors.lastname: Arase
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yoshimura
mesh_terms: D000107:Acetylation; D000818:Animals; D002875:Chromosomes / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D051548:Histone Acetyltransferases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008845:Microinjections; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D008938:Mitosis / Q000502:physiology*; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D050656:Transcription Factor AP-2 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000092468:Bromodomain Containing Proteins
chemical_list: D004791:Enzyme Inhibitors; D049452:Green Fluorescent Proteins; D051548:Histone Acetyltransferases; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C486694:Brd4 protein, mouse; D000092468:Bromodomain Containing Proteins; C485184:enhanced green fluorescent protein; C012589:trichostatin A