Effects of histone acetylation on the equilibrium accessibility of nucleosomal DNA target sites
Effects of histone acetylation on the equilibrium accessibility of nucleosomal DNA target sites
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DOI：
10.1006/jmbi.2001.4528
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发表时间：
2001-04-06
影响因子：
5.6
通讯作者：
Widom, J
中科院分区：
文献类型：
--
作者：
Anderson, JD;Lowary, PT;Widom, J
保守的核心组蛋白N-末端尾部结构域的翻译后乙酰化与基因激活有关，但涉及的分子机制尚不清楚。在早期的研究中，我们表明，通过胰蛋白酶蛋白水解完全去除尾部结构域（这使得核小体仍然完整）导致核小体DNA靶位点的动态平衡可达性增加1.5至14倍。这些观察结果表明，通过适度增加埋藏的DNA靶位点的平衡可及性，组蛋白乙酰化可以导致调节蛋白的占用增加，最终增加转录起始的概率。在这里，我们将这些观察扩展到一个更自然的系统，涉及完整的，但高度乙酰化的核小体。我们发现，组蛋白超乙酰化导致暴露核小体DNA靶位点的位置依赖性平衡常数增加1.1至1.8倍，平均增加1.4（+/-0.1）倍。这些结果的机制和生物学意义进行了讨论。(C)北京：科学出版社.
Posttranslational acetylation of the conserved core histone N-terminal tail domains is linked to gene activation, but the molecular mechanisms involved are not known. In an earlier study we showed that removing the tail domains altogether by trypsin proteolysis (which leaves nucleosomes nevertheless intact) leads to 1.5 to 14-fold increases in the dynamic equilibrium accessibility of nucleosomal DNA target sites. These observations suggested that, by modestly increasing the equilibrium accessibility of buried DNA target sites, histone acetylation could result in an increased occupancy by regulatory proteins, ultimately increasing the probability of transcription initiation. Here, we extend these observations to a more natural system involving intact but hyperacetylated nucleosomes. We find that histone hyperacetylation leads to 1.1 to 1.8-fold increases in position-dependent equilibrium constants for exposure of nucleosomal DNA target sites, with an average increase of 1.4(+/-0.1)-fold. The mechanistic and biological implications of these results are discussed. (C) 2001 Academic Press.