Author Yamashita M, Ukai-Tadenuma M, Miyamoto T, Sugaya K, Hosokawa H, Hasegawa A, Kimura M, Taniguchi M, DeGregori J, Nakayama T.
Title Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci.
Journal J. Biol. Chem.
Abstract GATA3 expression is essential for type-2 helper T (Th2) cell differentiation. GATA3-mediated chromatin remodeling at the Th2 cytokine gene loci, including Th2-specific long range histone hyperacetylation of the interleukin (IL)-13/IL-4 gene loci, occurs in developing Th2 cells. However, little is known about the role of GATA3, if any, in the maintenance of established remodeled chromatin at the Th2 cytokine gene loci. Here, we established a Cre/LoxP-based site-specific recombination system in cultured CD4 T cells using a unique adenovirus-mediated gene transfer technique. This system allowed us to investigate the effect of loss of GATA3 expression in in vitro differentiated Th2 cells. After ablation of GATA3, we detected reduced production of all Th2 cytokines, increased DNA methylation at the IL-4 gene locus, and decreased histone hyperacetylation at the IL-5 gene locus but not significantly so at the IL-13/IL-4 gene loci. Thus, GATA3 plays important roles in the maintenance of the Th2 phenotype and continuous chromatin remodeling of the specific Th2 cytokine gene locus through cell division.
Volume 279(26)
Pages 26983-90
Published 2004-6-25
DOI 10.1074/jbc.M403688200
PII M403688200
PMID 15087456
MeSH Acetylation Adenoviridae / genetics Animals CD4-Positive T-Lymphocytes / metabolism Cell Differentiation / physiology Chromatin / metabolism* Cytokines / biosynthesis* Cytokines / genetics DNA-Binding Proteins / biosynthesis DNA-Binding Proteins / genetics DNA-Binding Proteins / physiology* GATA3 Transcription Factor Gene Expression Green Fluorescent Proteins Histones / metabolism Humans Integrases / genetics Luminescent Proteins / genetics Mice Mice, Inbred C57BL Mice, Transgenic Recombination, Genetic Retroviridae / genetics Th2 Cells / immunology Th2 Cells / metabolism Th2 Cells / physiology* Trans-Activators / biosynthesis Trans-Activators / genetics Trans-Activators / physiology* Transgenes / genetics Viral Proteins / genetics
IF 4.011
Times Cited 107
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