Journal
EMBO JOURNAL
Volume 31, Issue 19, Pages 3809-3820Publisher
WILEY
DOI: 10.1038/emboj.2012.233
Keywords
brd4; bromodomain inhibitor; histone variants; infertility; JQ1
Categories
Funding
- ANR
- INCa-DHOS fund
- 'ARC libre' fund
- 'Region Rhone-Alpes' 'cible' grant
- ARC
- NIH [R01 GM081767]
- IBiSA
- Universite de la Mediterranee
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Male germ cell differentiation is a highly regulated multi-step 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 postmeiotic 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. The EMBO Journal (2012) 31, 3809-3820. doi:10.1038/emboj.2012.233; Published online 24 August 2012
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