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

Hiroyuki Hosokawa; Tomoaki Tanaka; Yutaka Suzuki; Chiaki Iwamura; Shuichi Ohkubo; Kanji Endoh; Miki Kato; Yusuke Endo; Atsushi Onodera; Damon John Tumes; Akinori Kanai; Sumio Sugano; Toshinori Nakayama

doi:10.1073/pnas.1220865110

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

Hiroyuki Hosokawa, Tomoaki Tanaka, Yutaka Suzuki, Chiaki Iwamura, Shuichi Ohkubo, Kanji Endoh, Miki Kato, Yusuke Endo, Atsushi Onodera, Damon John Tumes, Akinori Kanai, Sumio Sugano, Toshinori Nakayama

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

69 Citations (Scopus)

Abstract

GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naïve 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-γ. 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.

Original language	English
Pages (from-to)	4691-4696
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	110
Issue number	12
DOIs	https://doi.org/10.1073/pnas.1220865110
Publication status	Published or Issued - 19 Mar 2013
Externally published	Yes

Keywords

T helper 2 cell differentiation
Transcriptional regulation

ASJC Scopus subject areas

General

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10.1073/pnas.1220865110

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Hosokawa, H., Tanaka, T., Suzuki, Y., Iwamura, C., Ohkubo, S., Endoh, K., Kato, M., Endo, Y., Onodera, A., Tumes, D. J., Kanai, A., Sugano, S., & Nakayama, T. (2013). Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity. Proceedings of the National Academy of Sciences of the United States of America, 110(12), 4691-4696. https://doi.org/10.1073/pnas.1220865110

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

abstract = "GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of na{\"i}ve 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-γ. 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.",

keywords = "T helper 2 cell differentiation, Transcriptional regulation",

author = "Hiroyuki Hosokawa and Tomoaki Tanaka and Yutaka Suzuki and Chiaki Iwamura and Shuichi Ohkubo and Kanji Endoh and Miki Kato and Yusuke Endo and Atsushi Onodera and Tumes, {Damon John} and Akinori Kanai and Sumio Sugano and Toshinori Nakayama",

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doi = "10.1073/pnas.1220865110",

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Hosokawa, H, Tanaka, T, Suzuki, Y, Iwamura, C, Ohkubo, S, Endoh, K, Kato, M, Endo, Y, Onodera, A, Tumes, DJ, Kanai, A, Sugano, S & Nakayama, T 2013, 'Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 12, pp. 4691-4696. https://doi.org/10.1073/pnas.1220865110

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T1 - Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity

AU - Hosokawa, Hiroyuki

AU - Tanaka, Tomoaki

AU - Suzuki, Yutaka

AU - Iwamura, Chiaki

AU - Ohkubo, Shuichi

AU - Endoh, Kanji

AU - Kato, Miki

AU - Endo, Yusuke

AU - Onodera, Atsushi

AU - Tumes, Damon John

AU - Kanai, Akinori

AU - Sugano, Sumio

AU - Nakayama, Toshinori

PY - 2013/3/19

Y1 - 2013/3/19

N2 - GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naïve 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-γ. 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.

AB - GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naïve 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-γ. 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.

KW - T helper 2 cell differentiation

KW - Transcriptional regulation

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DO - 10.1073/pnas.1220865110

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AN - SCOPUS:84875279735

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JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 12

ER -

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

Abstract

Keywords

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