Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes

被引：194

作者：

Zamudio, Alicia V. ^{[1
,2
]}

Dall'Agnese, Alessandra ^{[1
]}

Henninger, Jonathan E. ^{[1
]}

Manteiga, John C. ^{[1
,2
]}

Afeyan, Lena K. ^{[1
,2
]}

Hannett, Nancy M. ^{[1
]}

Coffey, Eliot L. ^{[1
,2
]}

Li, Charles H. ^{[1
,2
]}

Oksuz, Ozgur ^{[1
]}

Sabari, Benjamin R. ^{[1
]}

Boija, Ann ^{[1
]}

Klein, Isaac A. ^{[1
,3
]}

Hawken, Susana W. ^{[4
]}

Spille, Jan-Hendrik ^{[5
]}

Decker, Tim-Michael ^{[6
]}

Cisse, Ibrahim I. ^{[5
]}

Abraham, Brian J. ^{[1
,7
]}

Lee, Tong I. ^{[1
]}

Taatjes, Dylan J. ^{[6
]}

Schuijers, Jurian ^{[1
,8
]}

Young, Richard A. ^{[1
,2
]}

机构：

[1] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA

[2] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[3] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[4] MIT, Program Computat & Syst Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[5] MIT, Dept Phys, Cambridge, MA 02139 USA

[6] Univ Colorado, Dept Biochem, Boulder, CO 80303 USA

[7] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA

[8] Univ Med Ctr Utrecht, Ctr Mol Med, NL-3584 CX Utrecht, Netherlands

来源：

MOLECULAR CELL | 2019年 / 76卷 / 05期

基金：

瑞典研究理事会; 美国国家科学基金会;

关键词：

MASTER TRANSCRIPTION FACTORS; LIQUID PHASE-SEPARATION; BETA-CATENIN; WNT/BETA-CATENIN; SUPER-ENHANCERS; FUNCTIONAL INTERACTION; ACTIVATION; PATHWAYS; IDENTIFICATION; EXPRESSION;

D O I：

10.1016/j.molcel.2019.08.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The gene expression programs that define the identity of each cell are controlled by master transcription factors (TFs) that bind cell-type-specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-separated condensates with the Mediator coactivator at super-enhancers. Here, we present evidence that signaling factors for the WNT, TGF-beta, and JAK/STAT pathways use their intrinsically disordered regions (IDRs) to enter and concentrate in Mediator condensates at super-enhancers. We show that the WNT coactivator beta-catenin interacts both with components of condensates and DNA-binding factors to selectively occupy super-enhancer-associated genes. We propose that the cell-type specificity of the response to signaling is mediated in part by the IDRs of the signaling factors, which cause these factors to partition into condensates established by the master TFs and Mediator at genes with prominent roles in cell identity.

引用

页码：753 / +

页数：20

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