气候变化领域集成服务门户(CCPortal): Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation

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DOI	10.1073/pnas.2024685118
	Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation
	Frank F.; Liu X.; Ortlund E.A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:30
英文摘要	The glucocorticoid receptor (GR) is a ligand-regulated transcription factor (TF) that controls the tissue- and gene-specific transactivation and transrepression of thousands of target genes. Distinct GR DNA-binding sequences with activating or repressive activities have been identified, but how they modulate transcription in opposite ways is not known. We show that GR forms phase-separated condensates that specifically concentrate known coregulators via their intrinsically disordered regions (IDRs) in vitro. A combination of dynamic, multivalent (between IDRs) and specific, stable interactions (between LxxLL motifs and the GR ligand-binding domain) control the degree of recruitment. Importantly, GR DNA binding directs the selective partitioning of coregulators within GR condensates such that activating DNAs cause enhanced recruitment of coactivators. Our work shows that condensation controls GR function by modulating coregulator recruitment and provides a mechanism for the up- and down-regulation of GR target genes controlled by distinct DNA recognition elements. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Glucocorticoid receptor \| biomolecular condensates \| transcriptional coregulators \| intrinsically disordered regions \| transcriptional regulation
语种	英语
scopus关键词	DNA; glucocorticoid receptor; glucocorticoid; glucocorticoid receptor; Article; biomolecular condensate; dimerization; DNA binding; DNA recognition element; down regulation; gene expression regulation; human; in vitro study; intrinsically disordered region; ligand binding; molecular recognition; protein domain; protein motif; protein protein interaction; transactivation; transcription initiation; upregulation; chemistry; gene expression regulation; metabolism; promoter region; protein multimerization; regulatory sequence; Gene Expression Regulation; Glucocorticoids; Humans; Promoter Regions, Genetic; Protein Multimerization; Receptors, Glucocorticoid; Regulatory Sequences, Nucleic Acid; Transcriptional Activation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251115
作者单位	Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, United States
推荐引用方式 GB/T 7714	Frank F.,Liu X.,Ortlund E.A.. Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation[J],2021,118(30).
APA	Frank F.,Liu X.,&Ortlund E.A..(2021).Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation.Proceedings of the National Academy of Sciences of the United States of America,118(30).
MLA	Frank F.,et al."Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation".Proceedings of the National Academy of Sciences of the United States of America 118.30(2021).