HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription
HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription
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DOI：
10.1016/j.molcel.2006.04.019
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发表时间：
2006-06-09
期刊：
影响因子：
16
通讯作者：
Hager, Gordon L.
中科院分区：
文献类型：
--
作者：
Qiu, Yi;Zhao, Yingming;Hager, Gordon L.
虽然组蛋白去乙酰化酶（HDACs）通常被视为辅阻遏物，我们表明，HDAC1作为糖皮质激素受体（GR）的辅激活剂。此外，细胞HDAC1的亚组分在与GR结合后被乙酰化，并且这种乙酰化事件与启动子活性的降低相关。HDAC1在抑制染色质是高度乙酰化的，而在转录活性染色质上发现的脱乙酰酶表现出低水平的乙酰化。纯化的HDAC 1的乙酰化使其去乙酰化酶活性失活，并且关键乙酰化位点的突变废除了HDAC 1在体内的功能。我们建议，激素激活的受体导致渐进的乙酰化HDAC1在体内，这反过来又抑制了酶的脱乙酰酶活性，并防止启动子激活所需的脱乙酰化事件。这些研究结果表明，HDAC1是所需的一些基因的诱导GR，这种激活剂的功能是动态调节乙酰化。
Although histone deacetylases (HDACs) are generally viewed as corepressors, we show that HDAC1 serves as a coactivator for the glucocorticoid receptor (GR). Furthermore, a subfraction of cellular HDAC1 is acetylated after association with the GR, and this acetylation event correlates with a decrease in promoter activity. HDAC1 in repressed chromatin is highly acetylated, while the deacetylase found on transcriptionally active chromatin manifests a low level of acetylation. Acetylation of purified HDAC1 inactivates its deacetylase activity, and mutation of the critical acetylation sites abrogates HDAC1 function in vivo. We propose that hormone activation of the receptor leads to progressive acetylation of HDAC1 in vivo, which in turn inhibits the deacetylase activity of the enzyme and prevents a deacetylation event that is required for promoter activation. These findings indicate that HDAC1 is required for the induction of some genes by the GR, and this activator function is dynamically modulated by acetylation.