Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation
Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation
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DOI：
10.1016/j.cell.2005.03.035
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发表时间：
2005-05-20
期刊：
影响因子：
64.5
通讯作者：
Moazed, D
中科院分区：
文献类型：
--
作者：
Liou, GG;Tanny, JC;Moazed, D
出芽酵母中沉默染色质结构域的组装涉及Sir2对组蛋白尾部的去乙酰化以及Sir3和Sir4蛋白与低乙酰化组蛋白尾部的关联。Sir2将去乙酰化与NAD水解结合，并合成代谢物o -乙酰基- adp核糖（AAR），但NAD水解或AAR的功能意义（如果有的话）尚不清楚。在这里，我们研究了Sir2、Sir3和Sir4蛋白彼此之间和组蛋白尾部的关联。我们的分析表明，组蛋白H4-赖氨酸16 （K16）的去乙酰化对体内沉默至关重要，在体外也对Sir3和Sir4与组蛋白H4肽的结合至关重要。此外，AAR本身促进Sir3的多个拷贝与Sir2/Sir4的关联，并诱导SIR复合体的剧烈结构重排。这些结果表明，Sir2活性通过组蛋白去乙酰化和AAR合成来调节SIR复合物的组装。
Assembly of silent chromatin domains in budding yeast involves the deacetylation of histone tails by Sir2 and the association of the Sir3 and Sir4 proteins with hypoacetylated histone tails. Sir2 couples deacetylation to NAD hydrolysis and the synthesis of a metabolite, O-acetyl-ADP-ribose (AAR), but the functional significance of NAD hydrolysis or AAR, if any, is unknown. Here we examine the association of the Sir2, Sir3, and Sir4 proteins with each other and histone tails. Our analysis reveals that deacetylation of histone H4-lysine 16 (K16), which is critical for silencing in vivo, is also critical for the binding of Sir3 and Sir4 to histone H4 peptides in vitro. Moreover, AAR itself promotes the association of multiple copies of Sir3 with Sir2/Sir4 and induces a dramatic structural rearrangement in the SIR complex. These results suggest that Sir2 activity modulates the assembly of the SIR complex through both histone deacetylation and AAR synthesis.