{"title":"Roles of intrinsically disordered protein regions in transcriptional regulation and genome organization.","authors":"Jiapei Miao, Shasha Chong","doi":"10.1016/j.gde.2024.102285","DOIUrl":null,"url":null,"abstract":"<p><p>Eukaryotic transcription is a complex process regulated by transcription factors (TFs), coactivators, and RNA polymerase machineries, many of which contain sizable intrinsically disordered regions (IDRs). Many TFs activate transcription through multivalent IDR-IDR interactions. Optimal levels of such multivalent interactions associated with appropriate IDR concentrations, interaction strengths, or interaction valencies are required for effective transcriptional activation. The interaction selectivity of IDRs is crucial for the precise regulation of transcription, and this selectivity is dependent on the IDR sequences. Furthermore, IDRs modulate gene expression by bringing chromatin sites together to form transcriptionally active chromatin hubs. Mutations in IDRs may cause dysregulation of their multivalent interactions, contributing to diseases, including cancers and neurodegenerative disorders. Understanding the effects of IDR-related mutations on transcription control and genome organization opens new opportunities for developing targeted therapeutic strategies. In this review, we discuss recent reports documenting important functions of IDRs in transcriptional regulation and their implications for human health and disease.</p>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"90 ","pages":"102285"},"PeriodicalIF":3.7000,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Genetics & Development","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.gde.2024.102285","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Eukaryotic transcription is a complex process regulated by transcription factors (TFs), coactivators, and RNA polymerase machineries, many of which contain sizable intrinsically disordered regions (IDRs). Many TFs activate transcription through multivalent IDR-IDR interactions. Optimal levels of such multivalent interactions associated with appropriate IDR concentrations, interaction strengths, or interaction valencies are required for effective transcriptional activation. The interaction selectivity of IDRs is crucial for the precise regulation of transcription, and this selectivity is dependent on the IDR sequences. Furthermore, IDRs modulate gene expression by bringing chromatin sites together to form transcriptionally active chromatin hubs. Mutations in IDRs may cause dysregulation of their multivalent interactions, contributing to diseases, including cancers and neurodegenerative disorders. Understanding the effects of IDR-related mutations on transcription control and genome organization opens new opportunities for developing targeted therapeutic strategies. In this review, we discuss recent reports documenting important functions of IDRs in transcriptional regulation and their implications for human health and disease.
期刊介绍:
Current Opinion in Genetics and Development aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed.
In Current Opinion in Genetics and Development we help the reader by providing in a systematic manner:
1. The views of experts on current advances in their field in a clear and readable form.
2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications.[...]
The subject of Genetics and Development is divided into six themed sections, each of which is reviewed once a year:
• Cancer Genomics
• Genome Architecture and Expression
• Molecular and genetic basis of disease
• Developmental mechanisms, patterning and evolution
• Cell reprogramming, regeneration and repair
• Genetics of Human Origin / Evolutionary genetics (alternate years)