Cross-talk between histone H3 tails produces cooperative nucleosome acetylation
Cross-talk between histone H3 tails produces cooperative nucleosome acetylation
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DOI：
10.1073/pnas.0804530105
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发表时间：
2008-11-25
影响因子：
11.1
通讯作者：
Shogren-Knaak, Michael A.
中科院分区：
文献类型：
--
作者：
Li, Shanshan;Shogren-Knaak, Michael A.
酵母 Spt-Ada-Gcn5-乙酰转移酶 (SAGA) 复合物对组蛋白的乙酰化已成为理解染色质翻译后修饰如何调节真核基因表达的范例。尽管如此，尚不清楚染色质底物的结构复杂性在多大程度上调节 SAGA 活性。通过使用染色质模型系统，我们发现 SAGA 介导的组蛋白乙酰化具有高度协作性（协作常数为 1.97 +/- 0.15），利用多个不连续核小体的结合来促进最大乙酰化活性。对各种染色质底物（包括含有新型不对称组蛋白八聚体的底物）的研究表明，只有当核小体内的两个 H3 组蛋白尾正确定向且未乙酰化时，才会发生这种协同作用。我们提出，通过这种双尾识别调节最大SAGA活性可以通过促进基因之间的协同核小体乙酰化来促进空间邻近基因的共调节。
Acetylation of histone proteins by the yeast Spt-Ada-Gcn5-acetyltansferase (SAGA) complex has served as a paradigm for understanding how posttranslational modifications of chromatin regulate eukaryotic gene expression. Nonetheless, it has been unclear to what extent the structural complexity of the chromatin substrate modulates SAGA activity. By using chromatin model systems, we have found that SAGA-mediated histone acetylation is highly cooperative (cooperativity constant of 1.97 +/- 0.15), employing the binding of multiple noncontiguous nucleosomes to facilitate maximal acetylation activity. Studies with various chromatin substrates, including those containing novel asymmetric histone octamers, indicate that this cooperativity occurs only when both H3 histone tails within a nucleosome are properly oriented and unacetylated. We propose that modulation of maximal SAGA activity through this dual-tail recognition could facilitate coregulation of spatially proximal genes by promoting cooperative nucleosome acetylation between genes.