title: Methylation of Gata3 protein at Arg-261 regulates transactivation of the Il5 gene in T helper 2 cells.
abstract: Gata3 acts as a master regulator for T helper 2 (Th2) cell differentiation by inducing chromatin remodeling of the Th2 cytokine loci, accelerating Th2 cell proliferation, and repressing Th1 cell differentiation. Gata3 also directly transactivates the interleukin-5 (Il5) gene via additional mechanisms that have not been fully elucidated. We herein identified a mechanism whereby the methylation of Gata3 at Arg-261 regulates the transcriptional activation of the Il5 gene in Th2 cells. Although the methylation-mimicking Gata3 mutant retained the ability to induce IL-4 and repress IFNγ production, the IL-5 production was selectively impaired. We also demonstrated that heat shock protein (Hsp) 60 strongly associates with the methylation-mimicking Gata3 mutant and negatively regulates elongation of the Il5 transcript by RNA polymerase II. Thus, arginine methylation appears to play a pivotal role in the organization of Gata3 complexes and the target gene specificity of Gata3.
authors: From the Department of Immunology.
authors: Hiroyuki
authors: H
authors: Hosokawa
authors: From the Department of Immunology.
authors: Miki
authors: M
authors: Kato
authors: From the Department of Immunology.
authors: Hiroyuki
authors: H
authors: Tohyama
authors: From the Department of Immunology.
authors: Yuuki
authors: Y
authors: Tamaki
authors: From the Department of Immunology.
authors: Yusuke
authors: Y
authors: Endo
authors: From the Department of Immunology.
authors: Motoko Y
authors: MY
authors: Kimura
authors: From the Department of Immunology.
authors: Damon John
authors: DJ
authors: Tumes
authors: Department of Medical Immunology.
authors: Shinichiro
authors: S
authors: Motohashi
authors: the Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, and.
authors: Masaki
authors: M
authors: Matsumoto
authors: the Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, and.
authors: Keiichi I
authors: KI
authors: Nakayama
authors: Department of Clinical Cell Biology, and Division of Endocrinology and Metabolism, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, CREST, Japan Science and Technology Agency, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors: Tomoaki
authors: T
authors: Tanaka
authors: From the Department of Immunology, CREST, Japan Science and Technology Agency, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan tnakayama@faculty.chiba-u.jp.
authors: Toshinori
authors: T
authors: Nakayama
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D047468:Immunoprecipitation; D015848:Interleukin-5 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D018834:Chaperonin 60; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C557066:Hspd1 protein, mouse; D015848:Interleukin-5; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D001120:Arginine
keywords: GATA transcription factor; Gata3; Hsp60; IL-5; T helper cells; Th2; post-translational modification (PTM); protein methylation; transcription factor