Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci.
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.
Yamashita
Masakatsu
M
PRESTO Project, Japan Science and Technology Corporation, Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
Ukai-Tadenuma
Maki
M
Miyamoto
Takeshi
T
Sugaya
Kaoru
K
Hosokawa
Hiroyuki
H
Hasegawa
Akihiro
A
Kimura
Motoko
M
Taniguchi
Masaru
M
DeGregori
James
J
Nakayama
Toshinori
T
D000107:Acetylation; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002843:Chromatin / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050990:GATA3 Transcription Factor; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006657:Histones / Q000378:metabolism; D006801:Humans; D019426:Integrases / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011995:Recombination, Genetic; D012190:Retroviridae / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019076:Transgenes / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
D002843:Chromatin; D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D006657:Histones; D008164:Luminescent Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases