A Role for Nuclear Actin in HDAC 1 and 2 Regulation.
A Role for Nuclear Actin in HDAC 1 and 2 Regulation.
复制标题
核肌动蛋白在 HDAC 1 和 2 调节中的作用。
DOI：
10.1038/srep28460
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发表时间：
2016
影响因子：
4.6
通讯作者：
deLanerolle,Primal
中科院分区：
文献类型：
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作者：
Serebryannyy,LeonidA;Cruz,ChristinaM;deLanerolle,Primal
已知I类组蛋白脱乙酰基酶（HDAC）可以从组蛋白尾部去除乙酰基。这释放了组蛋白尾部的正电荷，并允许DNA更紧密地缠绕，防止转录因子结合和基因激活。虽然HDAC蛋白的功能在生物化学和临床上都变得越来越明显，但这类蛋白如何调节仍然知之甚少。我们发现了一种新的核肌动蛋白和HDAC 1和HDAC 2之间的相互作用。核肌动蛋白以前已被证明与越来越多的核蛋白质，包括染色质重塑复合物，转录因子和RNA聚合酶相互作用。我们发现单体肌动蛋白能够结合I类HDAC复合物。此外，增加HeLa细胞核提取物中肌动蛋白的浓度能够抑制整体HDAC功能。相反，聚合核肌动蛋白增加HDAC活性和降低组蛋白乙酰化。此外，发现I类HDAC与核肌动蛋白之间的相互作用是活性依赖的。总之，我们的数据表明核肌动蛋白能够调节HDAC 1和2的活性。
Class I histone deacetylases (HDACs) are known to remove acetyl groups from histone tails. This liberates positive charges on the histone tail and allows for tighter winding of DNA, preventing transcription factor binding and gene activation. Although the functions of HDAC proteins are becoming apparent both biochemically and clinically, how this class of proteins is regulated remains poorly understood. We identified a novel interaction between nuclear actin and HDAC 1 and HDAC 2. Nuclear actin has been previously shown to interact with a growing list of nuclear proteins including chromatin remodeling complexes, transcription factors and RNA polymerases. We find that monomeric actin is able to bind the class I HDAC complex. Furthermore, increasing the concentration of actin in HeLa nuclear extracts was able to suppress overall HDAC function. Conversely, polymerizing nuclear actin increased HDAC activity and decreased histone acetylation. Moreover, the interaction between class I HDACs and nuclear actin was found to be activity dependent. Together, our data suggest nuclear actin is able to regulate HDAC 1 and 2 activity.