Purified histone acetyltransferase complexes stimulate HIV-1 transcription from preassembled nucleosomal arrays
Purified histone acetyltransferase complexes stimulate HIV-1 transcription from preassembled nucleosomal arrays
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DOI：
10.1073/pnas.95.22.12924
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发表时间：
1998-10-27
影响因子：
11.1
通讯作者：
Workman, JL
中科院分区：
文献类型：
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作者：
Steger, DJ;Eberharter, A;Workman, JL
蛋白质乙酰化与HIV-1基因转录调控有关。在这里，我们利用了四个天然组蛋白乙酰转移酶（HAT）复合物从酵母的活动，直接测试是否乙酰化调节HIV-1的转录在体外。HAT活性乙酰化组蛋白H3（佐贺、Ada和NuA 3）或H4（NuA 4）以乙酰CoA依赖性方式刺激HIV-1从预组装的核小体模板转录。HATs不影响HIV-1从无组蛋白DNA的转录，表明这些活性以染色质特异性方式起作用。对于Ada和NuA 4，我们证明了仅组蛋白的乙酰化介导增强的转录，这表明这些复合物至少部分地通过修饰组蛋白来促进转录。为了解决HAT复合物刺激转录的潜在机制，我们进行了限制性酶可及性分析。每一个HAT都以不需要转录的方式增加了靶向HIV-1染色质模板的限制性核酸内切酶的切割效率，这表明组蛋白乙酰化导致核小体重塑。
Protein acetylation has been implicated in the regulation of HIV-1 gene transcription. Here, we have exploited the activities of four native histone acetyltransferase (HAT) complexes from yeast to directly test whether acetylation regulates HIV-I transcription in vitro. HAT activities acetylating either histone H3 (SAGA, Ada, and NuA3) or H4 (NuA4) stimulate HIV-1 transcription from preassembled nucleosomal templates in an acetyl CoA-dependent manner. HIV-I transcription from histone-free DNA is not affected by the HATs, indicating that these activities function in a chromatin-specific fashion. For Ada and NuA4, we demonstrate that acetylation of only histone proteins mediates enhanced transcription, suggesting that these complexes facilitate transcription at least in part by modifying histones, To address a potential mechanism by which HAT complexes stimulate transcription, we performed a restriction enzyme accessibility analysis. Each of the HATs increases the cutting efficiencies of restriction endonucleases targeting the HIV-1 chromatin templates in a manner not requiring transcription, suggesting that histone acetylation leads to nucleosome remodeling.