Loponte Sara, Segré Chiara V, Senese Silvia, Miccolo Claudia, Santaguida Stefano, Deflorian Gianluca, Citro Simona, Mattoscio Domenico, Pisati Federica, Moser Mirjam A, Visintin Rosella, Seiser Christian, Chiocca Susanna
Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy.
The FIRC Institute for Molecular Oncology (IFOM), via Adamello 16, 20139 Milan, Italy.
Sci Rep. 2016 Jul 26;6:30213. doi: 10.1038/srep30213.
Histone deacetylases (HDACs) catalyze the removal of acetyl molecules from histone and non-histone substrates playing important roles in chromatin remodeling and control of gene expression. Class I HDAC1 is a critical regulator of cell cycle progression, cellular proliferation and differentiation during development; it is also regulated by many post-translational modifications (PTMs). Herein we characterize a new mitosis-specific phosphorylation of HDAC1 driven by Aurora kinases A and B. We show that this phosphorylation affects HDAC1 enzymatic activity and it is critical for the maintenance of a proper proliferative and developmental plan in a complex organism. Notably, we find that Aurora-dependent phosphorylation of HDAC1 regulates histone acetylation by modulating the expression of genes directly involved in the developing zebrafish central nervous system. Our data represent a step towards the comprehension of HDAC1 regulation by its PTM code, with important implications in unravelling its roles both in physiology and pathology.
组蛋白去乙酰化酶（HDACs）催化从组蛋白和非组蛋白底物上去除乙酰分子，在染色质重塑和基因表达控制中发挥重要作用。I类HDAC1是细胞周期进程、发育过程中细胞增殖和分化的关键调节因子；它也受到许多翻译后修饰（PTMs）的调控。在此，我们描述了一种由极光激酶A和B驱动的HDAC1新的有丝分裂特异性磷酸化。我们表明，这种磷酸化影响HDAC1的酶活性，对于复杂生物体中维持适当的增殖和发育计划至关重要。值得注意的是，我们发现HDAC1的极光激酶依赖性磷酸化通过调节直接参与斑马鱼中枢神经系统发育的基因表达来调节组蛋白乙酰化。我们的数据代表了朝着通过其PTM编码理解HDAC1调控迈出的一步，对阐明其在生理和病理中的作用具有重要意义。
