Abstract
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.
Highlights
Histone deacetylases (HDACs) are enzymes which remove acetyl moieties from ε-NH3 groups of lysines from both nucleosomal histones and non-histone proteins[1]; they are known as “lysine deacetylases” (K[Lys]DAC)[2]
To better analyze the appearance of this modified form of HDAC1 as cells proceeded towards mitosis, HeLa cells were synchronized at the G1/S boundary by a double thymidine block, released in fresh medium containing nocodazole and samples were collected every hour (Supplementary Fig. S1a)
The modified form of HDAC1 appeared after 7 hours, when cells started to enter mitosis and the maximum level of modification peaked at 9 hours corresponding to the maximal level of phospho-serine10-H3 (H3S10ph), a known marker of mitosis[28]
Summary
Histone deacetylases (HDACs) are enzymes which remove acetyl moieties from ε-NH3 groups of lysines from both nucleosomal histones and non-histone proteins[1]; they are known as “lysine deacetylases” (K[Lys]DAC)[2]. HDAC1 Aurora-dependent phosphorylation is critical for a proper developmental plan and controls the accurate cell cycle progression of zebrafish embryos.
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