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Bromodomain-dependent stage-specific male genome programming by Brdt
Article first published online: 24 AUG 2012
Copyright © 2012 European Molecular Biology Organization
The EMBO Journal
Volume 31, Issue 19, pages 3809–3820, October 3, 2012
How to Cite
Gaucher, J., Boussouar, F., Montellier, E., Curtet, S., Buchou, T., Bertrand, S., Hery, P., Jounier, S., Depaux, A., Vitte, A.-L., Guardiola, P., Pernet, K., Debernardi, A., Lopez, F., Holota, H., Imbert, J., Wolgemuth, D. J., Gérard, M., Rousseaux, S. and Khochbin, S. (2012), Bromodomain-dependent stage-specific male genome programming by Brdt. The EMBO Journal, 31: 3809–3820. doi: 10.1038/emboj.2012.233
- Issue published online: 3 OCT 2012
- Article first published online: 24 AUG 2012
- Manuscript Accepted: 10 AUG 2012
- Manuscript Received: 13 JUN 2012
- bromodomain inhibitor;
- histone variants;
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.