A Genomic Regulatory Element That Directs Assembly and Function of Immune-Specific AP-1-IRF Complexes

被引：280

作者：

Glasmacher, Elke ^{[2
]}

Agrawal, Smita ^{[2
]}

Chang, Abraham B. ^{[2
]}

Murphy, Theresa L. ^{[1
]}

Zeng, Wenwen ^{[2
]}

Vander Lugt, Bryan ^{[2
]}

Khan, Aly A. ^{[3
,4
]}

Ciofani, Maria ^{[5
]}

Spooner, Chauncey J. ^{[2
]}

Rutz, Sascha ^{[2
]}

Hackney, Jason ^{[6
]}

Nurieva, Roza ^{[7
]}

Escalante, Carlos R. ^{[8
]}

Ouyang, Wenjun ^{[2
]}

Littman, Dan R.

Murphy, Kenneth M. ^{[1
]}

Singh, Harinder ^{[2
]}

机构：

[1] Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol & Immunol, St Louis, MO 63110 USA

[2] Genentech Inc, Dept Discovery Immunol, San Francisco, CA 94080 USA

[3] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[4] Univ Chicago, Inst Syst & Genom Biol, Chicago, IL 60637 USA

[5] NYU, Howard Hughes Med Inst, Skirball Inst Biomol Med, New York, NY 10016 USA

[6] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77054 USA

[8] Virginia Commonwealth Univ, Sch Med, Dept Physiol & Biophys, Richmond, VA 23219 USA

来源：

SCIENCE | 2012年 / 338卷 / 6109期

关键词：

TRANSCRIPTION FACTOR IRF4; FACTOR BATF CONTROLS; CELL-DIFFERENTIATION; FAMILY; ACTIVATION; EXPRESSION; PROGRAM; ABSENCE; MEMBER; ROLES;

D O I：

10.1126/science.1228309

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Interferon regulatory factor 4 (IRF4) and IRF8 regulate B, T, macrophage, and dendritic cell differentiation. They are recruited to cis-regulatory Ets-IRF composite elements by PU.1 or Spi-B. How these IRFs target genes in most T cells is enigmatic given the absence of specific Ets partners. Chromatin immunoprecipitation sequencing in T helper 17 (T(H)17) cells reveals that IRF4 targets sequences enriched for activating protein 1 (AP-1)-IRF composite elements (AICEs) that are co-bound by BATF, an AP-1 factor required for T(H)17, B, and dendritic cell differentiation. IRF4 and BATF bind cooperatively to structurally divergent AICEs to promote gene activation and T(H)17 differentiation. The AICE motif directs assembly of IRF4 or IRF8 with BATF heterodimers and is also used in T(H)2, B, and dendritic cells. This genomic regulatory element and cognate factors appear to have evolved to integrate diverse immunomodulatory signals.

引用

页码：975 / 980

页数：6

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