Hu Jialei, Donahue Greg, Dorsey Jean, Govin Jérôme, Yuan Zuofei, Garcia Benjamin A, Shah Parisha P, Berger Shelley L
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Program, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Laboratoire Biologie à Grande Echelle, INSERM, U1038 Grenoble, France.
Cell Rep. 2015 Dec 1;13(9):1772-80. doi: 10.1016/j.celrep.2015.10.070. Epub 2015 Nov 25.
Meiotic recombination hotspots are associated with histone post-translational modifications and open chromatin. However, it remains unclear how histone modifications and chromatin structure regulate meiotic recombination. Here, we identify acetylation of histone H4 at Lys44 (H4K44ac) occurring on the nucleosomal lateral surface. We show that H4K44 is acetylated at pre-meiosis and meiosis and displays genome-wide enrichment at recombination hotspots in meiosis. Acetylation at H4K44 is required for normal meiotic recombination, normal levels of double-strand breaks (DSBs) during meiosis, and optimal sporulation. Non-modifiable H4K44R results in increased nucleosomal occupancy around DSB hotspots. Our results indicate that H4K44ac functions to facilitate chromatin accessibility favorable for normal DSB formation and meiotic recombination.
减数分裂重组热点与组蛋白翻译后修饰及开放染色质相关。然而,组蛋白修饰和染色质结构如何调控减数分裂重组仍不清楚。在此,我们鉴定出在核小体侧面发生的组蛋白H4赖氨酸44位点乙酰化(H4K44ac)。我们发现H4K44在减数分裂前和减数分裂期间被乙酰化,并且在减数分裂的重组热点处呈现全基因组富集。H4K44位点的乙酰化是正常减数分裂重组、减数分裂期间双链断裂(DSB)的正常水平以及最佳孢子形成所必需的。不可修饰的H4K44R会导致DSB热点周围核小体占据增加。我们的结果表明,H4K44ac的作用是促进有利于正常DSB形成和减数分裂重组的染色质可及性。