H2A monoubiquitination: insights from human genetics and animal models.

Autor: Ryan CW; Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI, 48109-5618, USA.; Medical Science Training Program, University of Michigan Medical School, 3703 Med Sci II, 1241 E. Catherine St., Ann Arbor, MI, 48109-5618, USA., Peirent ER; Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI, 48109-5618, USA., Regan SL; Department of Human Genetics, University of Michigan Medical School, 3703 Med Sci II, 1241 E. Catherine St., Ann Arbor, MI, 48109-5618, USA., Guxholli A; Department of Human Genetics, University of Michigan Medical School, 3703 Med Sci II, 1241 E. Catherine St., Ann Arbor, MI, 48109-5618, USA.; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, 48199-5618, USA., Bielas SL; Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI, 48109-5618, USA. sbielas@umich.edu.; Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI, 48109-5618, USA. sbielas@umich.edu.; Department of Human Genetics, University of Michigan Medical School, 3703 Med Sci II, 1241 E. Catherine St., Ann Arbor, MI, 48109-5618, USA. sbielas@umich.edu.; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, 48199-5618, USA. sbielas@umich.edu.
Jazyk: angličtina
Zdroj: Human genetics [Hum Genet] 2024 Apr; Vol. 143 (4), pp. 511-527. Date of Electronic Publication: 2023 Apr 22.
DOI: 10.1007/s00439-023-02557-x
Abstrakt: Metazoan development arises from spatiotemporal control of gene expression, which depends on epigenetic regulators like the polycomb group proteins (PcG) that govern the chromatin landscape. PcG proteins facilitate the addition and removal of histone 2A monoubiquitination at lysine 119 (H2AK119ub1), which regulates gene expression, cell fate decisions, cell cycle progression, and DNA damage repair. Regulation of these processes by PcG proteins is necessary for proper development, as pathogenic variants in these genes are increasingly recognized to underly developmental disorders. Overlapping features of developmental syndromes associated with pathogenic variants in specific PcG genes suggest disruption of central developmental mechanisms; however, unique clinical features observed in each syndrome suggest additional non-redundant functions for each PcG gene. In this review, we describe the clinical manifestations of pathogenic PcG gene variants, review what is known about the molecular functions of these gene products during development, and interpret the clinical data to summarize the current evidence toward an understanding of the genetic and molecular mechanism.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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