Polycomb group-mediated histone H2A monoubiquitination in epigenome regulation and nuclear processes

• Published in: Nature communications Vol. 11; no. 1; p. 5947
• Main Authors: Barbour, Haithem, Daou, Salima, Hendzel, Michael, Affar, El Bachir
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-11-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 38/15; 631/337; 631/337/176; 631/45; 631/67; 82/1; 82/80; 82/83; 96; 96/95; Animals; Chromatin; Chromatin - metabolism; Crosstalk; Deoxyribonucleic acid; Deposition; Deubiquitinating Enzymes - metabolism; DNA; DNA biosynthesis; DNA methylation; DNA repair; Drosophila; Epigenesis, Genetic; Fruit flies; Gene expression; Histone H2A; Histones; Histones - metabolism; Humanities and Social Sciences; Humans; Insects; Lysine; Methylation; multidisciplinary; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Polycomb group proteins; Polycomb-Group Proteins - chemistry; Polycomb-Group Proteins - genetics; Polycomb-Group Proteins - metabolism; Review; Review Article; Science; Science (multidisciplinary); Transcription; Ubiquitination; Vertebrates
• ISSN: 2041-1723; 2041-1723
• 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.
Histone H2A monoubiquitination on lysine 119 in vertebrate and lysine 118 in Drosophila (H2Aub) is an epigenomic mark usually associated with gene repression by Polycomb group factors. Here the authors review the current knowledge on the deposition and removal of H2Aub, its function in transcription and other DNA-associated processes as well as its relevance to human disease.