Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
J Biol Chem. 2012 Feb 3;287(6):4386-93. doi: 10.1074/jbc.M111.329417. Epub 2011 Dec 19.
Histone lysine acetylation has emerged as a key regulator of genome organization. However, with a few exceptions, the contribution of each acetylated lysine to cellular functions is not well understood because of the limited specificity of most histone acetyltransferases and histone deacetylases. Here we show that the Mst2 complex in Schizosaccharomyces pombe is a highly specific H3 lysine 14 (H3K14) acetyltransferase that functions together with Gcn5 to regulate global levels of H3K14 acetylation (H3K14ac). By analyzing the effect of H3K14ac loss through both enzymatic inactivation and histone mutations, we found that H3K14ac is critical for DNA damage checkpoint activation by directly regulating the compaction of chromatin and by recruiting chromatin remodeling protein complex RSC.
组蛋白赖氨酸乙酰化已成为基因组组织的关键调控因子。然而，由于大多数组蛋白乙酰转移酶和组蛋白去乙酰化酶的特异性有限，除了少数例外，每个乙酰化赖氨酸对细胞功能的贡献还不是很清楚。在这里，我们表明裂殖酵母中的 Mst2 复合物是一种高度特异性的 H3 赖氨酸 14（H3K14）乙酰转移酶，它与 Gcn5 一起调节 H3K14 乙酰化（H3K14ac）的整体水平。通过分析通过酶失活和组蛋白突变对 H3K14ac 缺失的影响，我们发现 H3K14ac 通过直接调节染色质的紧缩和募集染色质重塑蛋白复合物 RSC，对于 DNA 损伤检查点的激活至关重要。
