Maisonneuve-Rosemont Hospital Research Center and Department of Medicine, University of Montréal, Montréal, H3C 3J7, QC, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5G 1X5, Canada.
Nat Commun. 2020 Nov 23;11(1):5947. doi: 10.1038/s41467-020-19722-9.
Histone posttranslational modifications are key regulators of chromatin-associated processes including gene expression, DNA replication and DNA repair. Monoubiquitinated histone H2A, H2Aub (K118 in Drosophila or K119 in vertebrates) is catalyzed by the Polycomb group (PcG) repressive complex 1 (PRC1) and reversed by the PcG-repressive deubiquitinase (PR-DUB)/BAP1 complex. Here we critically assess the current knowledge regarding H2Aub deposition and removal, its crosstalk with PcG repressive complex 2 (PRC2)-mediated histone H3K27 methylation, and the recent attempts toward discovering its readers and solving its enigmatic functions. We also discuss mounting evidence of the involvement of H2A ubiquitination in human pathologies including cancer, while highlighting some knowledge gaps that remain to be addressed.
组蛋白翻译后修饰是染色质相关过程（包括基因表达、DNA 复制和 DNA 修复）的关键调节剂。单泛素化组蛋白 H2A、H2Aub（果蝇中的 K118 或脊椎动物中的 K119）由多梳抑制复合物 1（PRC1）催化，并由多梳抑制去泛素酶（PR-DUB）/BAP1 复合物逆转。在这里，我们批判性地评估了当前关于 H2Aub 沉积和去除、与 PcG 抑制复合物 2（PRC2）介导的组蛋白 H3K27 甲基化的串扰以及最近发现其阅读器和解密其神秘功能的尝试的知识。我们还讨论了 H2A 泛素化参与人类疾病（包括癌症）的越来越多的证据，同时强调了一些仍有待解决的知识空白。
