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Critical YxKxHxxxRP Motif in the C-Terminal Region of GATA3 for Its DNA Binding and Function¹

Ryo Shinnakasu^*, Masakatsu Yamashita^*, Kenta Shinoda^*, Yusuke Endo^*, Hiroyuki Hosokawa^*, Akihiro Hasegawa^*, Shinji Ikemizu and Toshinori Nakayama^2,*

^* Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan; and Division of Structural Biology, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan

A zinc finger transcription factor, GATA3, plays an essential role in the development of T cells and the functional differentiation into type 2 Th cells. Two transactivation domains and two zinc finger regions are known to be important for the GATA3 function, whereas the role for other regions remains unclear. In this study we demonstrated that a conserved YxKxHxxxRP motif (aa 345–354) adjacent to the C-terminal zinc finger domain of GATA3 plays a critical in its DNA binding and functions, including transcriptional activity, the ability to induce chromatin remodeling of the Th2 cytokine gene loci, and Th2 cell differentiation. A single point mutation of the key amino acid (Y, K, H, R, and P) in the motif abrogated GATA3 functions. A computer simulation analysis based on the solution structure of the chicken GATA1/DNA complex supported the importance of this motif in GATA3 DNA binding. Thus, we identified a novel conserved YxKxHxxxRP motif adjacent to the C-terminal zinc finger domain of GATA3 that is indispensable for GATA3 DNA binding and functions.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants-in-Aid for Scientific Research in Priority Areas 17016010 and 17047007; Scientific Research B 17390139, Scientific Research C 18590466; Grant-in-Aid for Young Scientists 17790318; and Special Coordination Funds for Promoting Science and Technology), the Ministry of Health, Labor and Welfare (Japan), the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Immovation (Japan), The Japan Health Science Foundation, Kanae Foundation, Uehara Memorial Foundation, and Mochida Foundation.

² Address correspondence and reprint requests to Dr. Toshinori Nakayama, Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 Japan. E-mail address: tnakayama{at}faculty.chiba-u.jp

³ Abbreviations used in this paper: CGRE, conserved GATA3 response element; ChIP, chromatin immunoprecipitation; HEK 293, human embryonic kidney 293; hNGFR, human nerve growth factor receptor p75.

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