Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity

被引：71

作者：

Hosokawa, Hiroyuki ^{[1
]}

Tanaka, Tomoaki ^{[2
,3
,4
]}

Suzuki, Yutaka ^{[5
]}

Iwamura, Chiaki ^{[1
]}

Ohkubo, Shuichi ^{[6
]}

Endoh, Kanji ^{[6
]}

Kato, Miki ^{[1
]}

Endo, Yusuke ^{[1
]}

Onodera, Atsushi ^{[1
]}

Tumes, Damon John ^{[1
]}

Kanai, Akinori ^{[5
]}

Sugano, Sumio ^{[5
]}

Nakayama, Toshinori ^{[1
,4
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba 2608670, Japan

[2] Chiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chiba 2608670, Japan

[3] Chiba Univ, Grad Sch Med, Div Endocrinol & Metab, Chiba 2608670, Japan

[4] Japan Sci & Technol Agcy, CREST, Chiba 2608670, Japan

[5] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Chiba 2778562, Japan

[6] Taiho Pharmaceut Co Ltd, Tsukuba Res Ctr, Ibaraki 3002611, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 12期

关键词：

T helper 2 cell differentiation; transcriptional regulation; CHROMATIN REMODELER MI-2-BETA; HELPER TYPE-2 CELLS; TRANSCRIPTION FACTOR; T-BET; GENE-EXPRESSION; TARGET GENES; GATA-3; DIFFERENTIATION; MAINTENANCE;

D O I：

10.1073/pnas.1220865110

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naive CD4 T cells into T helper 2 (Th2) cells. However, it is unknown how Gata3 simultaneously activates Th2-specific genes while repressing those of other Th lineages. Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFN-gamma. We define a Gata3/Chd4/p300 transcriptional activation complex at the Th2 cytokine loci and a Gata3/Chd4-nucleosome remodeling histone deacetylase repression complex at the Tbx21 locus in Th2 cells. We also demonstrate a physiological role for Chd4 in Th2-dependent inflammation in an in vivo model of asthmatic inflammation. Thus, Gata3/Chd4 forms functionally distinct complexes, which mediate both positive and negative gene regulation to facilitate Th2 cell differentiation.

引用

页码：4691 / 4696

页数：6

共 33 条

[1]

Developmental control via GATA factor interplay at chromatin domains [J].