Li Shanshan, Shogren-Knaak Michael A
Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18243-8. doi: 10.1073/pnas.0804530105. Epub 2008 Nov 12.
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.
酵母Spt-Ada-Gcn5-乙酰转移酶（SAGA）复合物对组蛋白的乙酰化作用，已成为理解染色质的翻译后修饰如何调控真核基因表达的范例。然而，染色质底物的结构复杂性在多大程度上调节SAGA活性尚不清楚。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同性（协同常数为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。对各种染色质底物的研究，包括那些含有新型不对称组蛋白八聚体的底物，表明这种协同性仅在核小体内的两条H3组蛋白尾巴正确定向且未被乙酰化时才会发生。我们提出，通过这种双尾识别对最大SAGA活性的调节，可通过促进基因间的协同核小体乙酰化来促进空间上相邻基因的共调节。
