title: Characterization of BRD4 during mammalian postmeiotic sperm development.
abstract: During spermiogenesis, the postmeiotic phase of mammalian spermatogenesis, transcription is progressively repressed as nuclei of haploid spermatids are compacted through a dramatic chromatin reorganization involving hyperacetylation and replacement of most histones with protamines. Although BRDT functions in transcription and histone removal in spermatids, it is unknown whether other BET family proteins play a role. Immunofluorescence of spermatogenic cells revealed BRD4 in a ring around the nuclei of spermatids containing hyperacetylated histones. The ring lies directly adjacent to the acroplaxome, the cytoskeletal base of the acrosome, previously linked to chromatin reorganization. The BRD4 ring does not form in acrosomal mutant mice. Chromatin immunoprecipitation followed by sequencing in spermatids revealed enrichment of BRD4 and acetylated histones at the promoters of active genes. BRD4 and BRDT show distinct and synergistic binding patterns, with a pronounced enrichment of BRD4 at spermatogenesis-specific genes. Direct association of BRD4 with acetylated H4 decreases in late spermatids as acetylated histones are removed from the condensing nucleus in a wave following the progressing acrosome. These data provide evidence of a prominent transcriptional role for BRD4 and suggest a possible removal mechanism for chromatin components from the genome via the progressing acrosome as transcription is repressed and chromatin is compacted during spermiogenesis.
authors.affiliation: Penn Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Biomedical Graduate Studies, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Bryant
authors.affiliation: Penn Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Donahue
authors.affiliation: Penn Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Xiaoshi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Mirella
authors.initials: M
authors.lastname: Meyer-Ficca
authors.affiliation: Penn Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Lacey J
authors.initials: LJ
authors.lastname: Luense
authors.affiliation: Penn Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Angela H
authors.initials: AH
authors.lastname: Weller
authors.affiliation: Penn Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Marisa S
authors.initials: MS
authors.lastname: Bartolomei
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Blobel
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Meyer
authors.affiliation: Penn Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
authors.affiliation: Penn Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA bergers@mail.med.upenn.edu.
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
mesh_terms: D000107:Acetylation; D000177:Acrosome / Q000378:metabolism / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000032:analysis / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013087:Spermatids / Q000166:cytology* / Q000378:metabolism; D013091:Spermatogenesis; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors; C486694:Brd4 protein, mouse; D000092468:Bromodomain Containing Proteins