Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 12, Pages 4691-4696Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1220865110
Keywords
T helper 2 cell differentiation; transcriptional regulation
Categories
Funding
- Global Center for Education and Research in Immune System Regulation and Treatment (Ministry of Education, Culture, Sports, Science, and Technology, Japan)
- Takeda Science Foundation
- Sagawa Cancer Foundation
- Astellas Foundation for Research on Metabolic Disorders
- Naito Foundation Natural Science Scholarship
- Princess Takamatsu Cancer Research Foundation
- Ichiro Kanehara Foundation
- Uehara Memorial Foundation
- Mitsukoshi Health and Welfare Foundation Research Fund
- [17016010]
- [20012010]
- [221S0002]
- [24116506]
- [21390147]
- [22300325]
- [24390239]
- [19659121]
- [20790367]
- Grants-in-Aid for Scientific Research [24390239, 24116506, 24790461, 221S0002, 23659240, 25670438, 22591093, 22300325, 23790523] Funding Source: KAKEN
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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.
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