H2A monoubiquitination: insights from human genetics and animal models.

IF 3.8 2区 生物学 Q2 GENETICS & HEREDITY
Human Genetics Pub Date : 2024-04-01 Epub Date: 2023-04-22 DOI:10.1007/s00439-023-02557-x
Charles W Ryan, Emily R Peirent, Samantha L Regan, Alba Guxholli, Stephanie L Bielas
{"title":"H2A monoubiquitination: insights from human genetics and animal models.","authors":"Charles W Ryan, Emily R Peirent, Samantha L Regan, Alba Guxholli, Stephanie L Bielas","doi":"10.1007/s00439-023-02557-x","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s00439-023-02557-x","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/4/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

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.

H2A 单泛素化:人类遗传学和动物模型的启示。
后生动物的发育源于基因表达的时空控制,而基因表达的时空控制依赖于像多聚酶群蛋白(PcG)这样的表观遗传调控因子,它们控制着染色质景观。PcG 蛋白促进组蛋白 2A 在赖氨酸 119(H2AK119ub1)处的单泛素化的添加和去除,从而调控基因表达、细胞命运决定、细胞周期进展和 DNA 损伤修复。PcG 蛋白对这些过程的调控是正常发育所必需的,因为这些基因中的致病变体越来越多地被认为是发育障碍的基础。与特定 PcG 基因致病变异相关的发育综合征的重叠特征表明,中心发育机制受到了干扰;然而,在每种综合征中观察到的独特临床特征表明,每个 PcG 基因都具有额外的非冗余功能。在这篇综述中,我们描述了致病性 PcG 基因变异的临床表现,回顾了目前已知的这些基因产物在发育过程中的分子功能,并对临床数据进行了解读,以总结目前的证据,从而了解遗传和分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Human Genetics
Human Genetics 生物-遗传学
CiteScore
10.80
自引率
3.80%
发文量
94
审稿时长
1 months
期刊介绍: Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信