Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity
Date
2013
Authors
Hosokawa, H.
Tanaka, T.
Suzuki, Y.
Iwamura, C.
Ohkubo, S.
Endoh, K.
Kato, M.
Endo, Y.
Onodera, A.
Tumes, D.J.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2013; 110(12):4691-4696
Statement of Responsibility
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
Copyright 2013 National Academy of Sciences
Access Condition Notes: This article is free to read online