Polycomb-dependent histone H2A ubiquitination links developmental disorders with cancer
- PMID: 34426021
- DOI: 10.1016/j.tig.2021.07.011
Polycomb-dependent histone H2A ubiquitination links developmental disorders with cancer
Abstract
Cell identity is tightly controlled by specific transcriptional programs which require post-translational modifications of histones. These histone modifications allow the establishment and maintenance of active and repressed chromatin domains. Histone H2A lysine 119 ubiquitination (H2AK119ub1) has an essential role in building repressive chromatin domains during development. It is regulated by the counteracting activities of the Polycomb repressive complex 1 (PRC1) and the Polycomb repressive-deubiquitinase (PR-DUB) complexes, two multi-subunit ensembles that write and erase this modification, respectively. We have catalogued the recurrent genetic alterations in subunits of the PRC1 and PR-DUB complexes in both neurodevelopmental disorders and cancer. These genetic lesions are often shared across disorders, and we highlight common mechanisms of H2AK119ub1 dysregulation and how they affect development in multiple disease contexts.
Keywords: Polycomb repressive complex 1 (PRC1); Polycomb repressive-deubiquitinase (PR-DUB) complex; cancer; chromatin; epigenetics; neurodevelopment; transcription.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of interests The authors declare no conflicts of interest.
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