The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in TH 2 cells

Shinya Tanaka; Yasutaka Motomura; Yoshie Suzuki; Ryoji Yagi; Hiromasa Inoue; Shoichiro Miyatake; Masato Kubo

doi:10.1038/ni.1966

The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in T_H 2 cells

Shinya Tanaka, Yasutaka Motomura, Yoshie Suzuki, Ryoji Yagi, Hiromasa Inoue, Shoichiro Miyatake, Masato Kubo

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

GATA-3 is a master regulator of T helper type 2 (T_H2) 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.

Original language	English
Pages (from-to)	77-85
Number of pages	9
Journal	Nature Immunology
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/ni.1966
Publication status	Published - Jan 2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

Access to Document

10.1038/ni.1966

Cite this

@article{a900c7cbde2f402c9e9b27f2348915ee,

title = "The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in TH 2 cells",

abstract = "GATA-3 is a master regulator of T helper type 2 (TH2) differentiation. However, the molecular basis of GATA-3-mediated TH 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 TH 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.",

author = "Shinya Tanaka and Yasutaka Motomura and Yoshie Suzuki and Ryoji Yagi and Hiromasa Inoue and Shoichiro Miyatake and Masato Kubo",

note = "Funding Information: We thank R. Locksley (University of California, San Francisco) for CNS-1-deficient mice on the BALB/c background; R. Abe (Tokyo University of Science) for the PV-1 mAb to CD28; T. Kitamura (Tokyo University) for Platinum-E packaging cells; and H. Fujimoto, Y. Hachiman, E. Hayashi and K. Ikari for technical assistance. Supported by a Grant-in-Aid-of-Scientific Research in Priority Areas of the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation; and RIKEN (Y.M.).",

year = "2011",

month = jan,

doi = "10.1038/ni.1966",

language = "English",

volume = "12",

pages = "77--85",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in TH 2 cells

AU - Tanaka, Shinya

AU - Motomura, Yasutaka

AU - Suzuki, Yoshie

AU - Yagi, Ryoji

AU - Inoue, Hiromasa

AU - Miyatake, Shoichiro

AU - Kubo, Masato

N1 - Funding Information: We thank R. Locksley (University of California, San Francisco) for CNS-1-deficient mice on the BALB/c background; R. Abe (Tokyo University of Science) for the PV-1 mAb to CD28; T. Kitamura (Tokyo University) for Platinum-E packaging cells; and H. Fujimoto, Y. Hachiman, E. Hayashi and K. Ikari for technical assistance. Supported by a Grant-in-Aid-of-Scientific Research in Priority Areas of the Ministry of Education, Culture, Sports, Science, and Technology of Japan; the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation; and RIKEN (Y.M.).

PY - 2011/1

Y1 - 2011/1

N2 - GATA-3 is a master regulator of T helper type 2 (TH2) differentiation. However, the molecular basis of GATA-3-mediated TH 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 TH 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.

AB - GATA-3 is a master regulator of T helper type 2 (TH2) differentiation. However, the molecular basis of GATA-3-mediated TH 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 TH 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.

UR - http://www.scopus.com/inward/record.url?scp=78650304399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650304399&partnerID=8YFLogxK

U2 - 10.1038/ni.1966

DO - 10.1038/ni.1966

M3 - Article

C2 - 21131966

AN - SCOPUS:78650304399

SN - 1529-2908

VL - 12

SP - 77

EP - 85

JO - Nature Immunology

JF - Nature Immunology

IS - 1

ER -

The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in T_H 2 cells

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this