Critical YxKxHxxxRP motif in the C-terminal region of GATA3 for its DNA binding and function
Critical YxKxHxxxRP motif in the C-terminal region of GATA3 for its DNA binding and function
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DOI：
10.4049/jimmunol.177.9.5801
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发表时间：
2006-11-01
影响因子：
4.4
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
--
作者：
Shinnakasu, Ryo;Yamashita, Masakatsu;Nakayama, Toshinori
锌指转录因子GATA 3在T细胞的发育和向2型Th细胞的功能分化中起重要作用。已知两个反式激活结构域和两个锌指区域对GATA 3功能很重要，而其他区域的作用尚不清楚。在这项研究中，我们证明了一个保守的YxKxHxxxRP基序（aa 345-354）相邻的C-末端锌指结构域的GATA 3发挥关键的DNA结合和功能，包括转录活性，诱导染色质重塑的Th 2细胞因子基因座的能力，和Th 2细胞分化。基序中关键氨基酸（Y、K、H、R和P）的单点突变废除了GATA 3功能。基于鸡GATA 1/DNA复合物的溶液结构的计算机模拟分析支持该基序在GATA 3 DNA结合中的重要性。因此，我们确定了一个新的保守的YxKxHxxxRP基序相邻的C-末端锌指结构域的GATA 3是必不可少的GATA 3 DNA结合和功能。
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.