title: Bromodomain-dependent stage-specific male genome programming by Brdt.
abstract: Male germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program. In meiotic and post-meiotic cells, Brdt initiates a genuine histone acetylation-guided programming of the genome by activating essential genes and repressing a 'progenitor cells' gene expression program. At post-meiotic stages, a global chromatin hyperacetylation gives the signal for Brdt's first bromodomain to direct the genome-wide replacement of histones by transition proteins. Brdt is therefore a unique and essential regulator of male germ cell differentiation, which, by using various domains in a developmentally controlled manner, first drives a specific spermatogenic gene expression program, and later controls the tight packaging of the male genome.
authors.affiliation: INSERM, U823, Université Joseph Fourier-Grenoble 1, Institut Albert Bonniot, Grenoble, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gaucher
authors.forename: Fayçal
authors.initials: F
authors.lastname: Boussouar
authors.forename: Emilie
authors.initials: E
authors.lastname: Montellier
authors.forename: Sandrine
authors.initials: S
authors.lastname: Curtet
authors.forename: Thierry
authors.initials: T
authors.lastname: Buchou
authors.forename: Sarah
authors.initials: S
authors.lastname: Bertrand
authors.forename: Patrick
authors.initials: P
authors.lastname: Hery
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jounier
authors.forename: Arnaud
authors.initials: A
authors.lastname: Depaux
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Vitte
authors.forename: Philippe
authors.initials: P
authors.lastname: Guardiola
authors.forename: Karin
authors.initials: K
authors.lastname: Pernet
authors.forename: Alexandra
authors.initials: A
authors.lastname: Debernardi
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lopez
authors.forename: Hélène
authors.initials: H
authors.lastname: Holota
authors.forename: Jean
authors.initials: J
authors.lastname: Imbert
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Wolgemuth
authors.forename: Matthieu
authors.initials: M
authors.lastname: Gérard
authors.forename: Sophie
authors.initials: S
authors.lastname: Rousseaux
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D016678:Genome / Q000502:physiology; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000254:growth & development / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
chemical_list: D051548:Histone Acetyltransferases; D006657:Histones; D009687:Nuclear Proteins; C518475:BRDT protein, mouse; D000092468:Bromodomain Containing Proteins