The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in TH2 cells

被引：106

作者：

Tanaka, Shinya ^{[1
]}

Motomura, Yasutaka ^{[1
]}

Suzuki, Yoshie ^{[1
]}

Yagi, Ryoji ^{[1
]}

Inoue, Hiromasa ^{[2
]}

Miyatake, Shoichiro ^{[3
]}

Kubo, Masato ^{[1
,4
]}

机构：

[1] RIKEN Yokohama Inst, Lab Signal Network, Res Ctr Allergy & Immunol, Yokohama, Kanagawa, Japan

[2] Kyushu Univ, Res Inst Dis Chest, Grad Sch Med Sci, Fukuoka 812, Japan

[3] Tokyo Metropolitan Inst Med Sci, Cytokine Project, Tokyo 113, Japan

[4] Tokyo Univ Sci, Res Inst Biol Sci, Chiba, Japan

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 01期

关键词：

LOCUS-CONTROL REGION; RANGE INTRACHROMOSOMAL INTERACTIONS; CYTOKINE GENE-EXPRESSION; HELPER T-CELLS; IL-4; GENE; CUTTING EDGE; COORDINATE REGULATOR; HISTONE ACETYLATION; TH2; DEVELOPMENT; FACTOR GATA-3;

D O I：

10.1038/ni.1966

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

GATA-3 is a master regulator of T helper type 2 (T(H)2) differentiation. However, the molecular basis of GATA-3-mediated T(H)2 lineage commitment is poorly understood. Here we identify the DNase I-hypersensitive site 2 (HS2) element located in the second intron of the interleukin 4 locus (Il4) as a critical enhancer strictly controlled by GATA-3 binding. Mice lacking HS2 showed substantial impairment in their asthmatic responses and their production of IL-4 but not of other T(H)2 cytokines. Overexpression of Gata3 in HS2-deficient T cells failed to restore Il4 expression. HS2 deletion impaired the trimethylation of histone H3 at Lys4 and acetylation of histone H3 at Lys9 and Lys14 in the Il4 locus. Our results indicate that HS2 is the target of GATA-3 in regulating chromosomal modification of the Il4 locus and is independent of the Il5 and Il13 loci.

引用

页码：77 / U103

页数：10

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