Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters

作者：Afsaneh Goudarzi, Di Zhang, He Huang, Sophie Barral, Oh Kwang Kwon, Shankang Qi, Zhanyun Tang, Thierry Buchou, Anne-Laure Vitte, HE Tie-ming, Zhongyi Cheng, Emilie Montellier, Jonathan Gaucher, Sandrine Curtet, Alexandra Debernardi, Guillaume Charbonnier, Denis Puthier, Carlo Petosa, Daniel Panne, Sophie Rousseaux, R G Roeder, Yingming Zhao, Saadi Khochbin · 发表于：Molecular Cell · 年份：2016 · DOI：10.1016/j.molcel.2016.03.014 · 被引用次数：275 · 研究领域：Genomics and Chromatin Dynamics、Histone Deacetylase Inhibitors Research、Epigenetics and DNA Methylation

Recently discovered histone lysine acylation marks increase the functional diversity of nucleosomes well beyond acetylation. Here, we focus on histone butyrylation in the context of sperm cell differentiation. Specifically, we investigate the butyrylation of histone H4 lysine 5 and 8 at gene promoters where acetylation guides the binding of Brdt, a bromodomain-containing protein, thereby mediating stage-specific gene expression programs and post-meiotic chromatin reorganization. Genome-wide mapping data show that highly active Brdt-bound gene promoters systematically harbor competing histone acetylation and butyrylation marks at H4 K5 and H4 K8. Despite acting as a direct stimulator of transcription, histone butyrylation competes with acetylation, especially at H4 K5, to prevent Brdt binding. Additionally, H4 K5K8 butyrylation also marks retarded histone removal during late spermatogenesis. Hence, alternating H4 acetylation and butyrylation, while sustaining direct gene activation and dynamic bromodomain binding, could impact the final male epigenome features.