Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate
Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate
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DOI：
10.1073/pnas.0909169107
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发表时间：
2010-03-23
影响因子：
11.1
通讯作者：
Ehrenhofer-Murray, Ann E.
中科院分区：
文献类型：
--
作者：
Ehrentraut, Stefan;Weber, Jan M.;Ehrenhofer-Murray, Ann E.
到目前为止，常染色质和异染色质区域之间的边界与染色质开放活动有关。在这里，我们确定了一个意想不到的作用，组蛋白去乙酰化在这个过程中。值得注意的是，组蛋白去乙酰化酶（HDAC）Rpd 3是必要的边界形成在酿酒酵母。rpd3。导致沉默信息调节子（SIR）的传播和亚端粒基因的抑制。在没有已知的边界因子的情况下，组蛋白乙酰转移酶复合物SAS-I，rpd 3。导致不适当的SIR传播，这对酵母细胞是致命的。值得注意的是，Rpd 3能够在靶向异染色质时产生边界。我们的数据表明了一种边界形成机制，即通过Rpd 3的组蛋白脱乙酰化去除HDAC Sir 2的底物，使得Sir 2不再能够通过在脱乙酰化反应中消耗NAD（+）来产生O-乙酰基-ADP核糖（OAADPR）。本质上，OAADPR因此不可用于绑定到Sir 3，从而防止SIR传播。
Boundaries between euchromatic and heterochromatic regions until now have been associated with chromatin-opening activities. Here, we identified an unexpected role for histone deacetylation in this process. Significantly, the histone deacetylase (HDAC) Rpd3 was necessary for boundary formation in Saccharomyces cerevisiae. rpd3. led to silent information regulator (SIR) spreading and repression of subtelomeric genes. In the absence of a known boundary factor, the histone acetyltransferase complex SAS-I, rpd3. caused inappropriate SIR spreading that was lethal to yeast cells. Notably, Rpd3 was capable of creating a boundary when targeted to heterochromatin. Our data suggest a mechanism for boundary formation whereby histone deacetylation by Rpd3 removes the substrate for the HDAC Sir2, so that Sir2 no longer can produce O-acetyl-ADP ribose (OAADPR) by consumption of NAD(+) in the deacetylation reaction. In essence, OAADPR therefore is unavailable for binding to Sir3, preventing SIR propagation.