Histone H2bub1 Deubiquitylation Is Essential for Mouse Development, but Does Not Regulate Global RNA Polymerase II Transcription
Cell Death & Differentiation (2021) 28:2385–2403 https://doi.org/10.1038/s41418-021-00759-2 ARTICLE Histone H2Bub1 deubiquitylation is essential for mouse development, but does not regulate global RNA polymerase II transcription 1,2,3,4 1,2,3,4,6 1,2,3,4,5 1,2,3,4 1,2,3,4 Fang Wang ● Farrah El-Saafin ● Tao Ye ● Matthieu Stierle ● Luc Negroni ● 1,2,3,4 1,2,3,4 1,2,3,4 1,2,3,4 1,2,3,4 Matej Durik ● Veronique Fischer ● Didier Devys ● Stéphane D. Vincent ● László Tora Received: 7 July 2020 / Revised: 18 February 2021 / Accepted: 23 February 2021 / Published online: 17 March 2021 © The Author(s) 2021. This article is published with open access Abstract Co-activator complexes dynamically deposit post-translational modifications (PTMs) on histones, or remove them, to regulate chromatin accessibility and/or to create/erase docking surfaces for proteins that recognize histone PTMs. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved multisubunit co-activator complex with modular organization. The deubiquitylation module (DUB) of mammalian SAGA complex is composed of the ubiquitin-specific protease 22 (USP22) and three adaptor proteins, ATXN7, ATXN7L3 and ENY2, which are all needed for the full activity of 1234567890();,: 1234567890();,: the USP22 enzyme to remove monoubiquitin (ub1) from histone H2B. Two additional USP22-related ubiquitin hydrolases (called USP27X or USP51) have been described to form alternative DUBs with ATXN7L3 and ENY2, which can also deubiquitylate H2Bub1. Here we report that USP22 and ATXN7L3 are essential for normal embryonic development of mice, however their requirements are not identical during this process, as Atxn7l3−/− embryos show developmental delay already at embryonic day (E) 7.5, while Usp22−/− embryos are normal at this stage, but die at E14.5.
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