The Enhancer HS2 Critically Regulates GATA-3-mediated Il4 Transcription in T(H)2 Cells

Overview

Journal Nat Immunol

Date 2010 Dec 7

PMID 21131966

Citations 73

Authors

Shinya Tanaka

Yasutaka Motomura

Yoshie Suzuki

Ryoji Yagi

Hiromasa Inoue

Shoichiro Miyatake

Masato Kubo

Affiliations

Soon will be listed here.

Abstract

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.

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