Critical YxKxHxxxRP motif in the C-terminal region of GATA3 for its DNA binding and function.
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.
Shinnakasu
Ryo
R
Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Yamashita
Masakatsu
M
Shinoda
Kenta
K
Endo
Yusuke
Y
Hosokawa
Hiroyuki
H
Hasegawa
Akihiro
A
Ikemizu
Shinji
S
Nakayama
Toshinori
T
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation; D011485:Protein Binding; D018418:Th2 Cells / Q000276:immunology*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D004247:DNA