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Lymphoid enhancer factor interacts with GATA‐3 and controls its function in T helper type 2 cells
Author(s) -
Hossain Mohammad B.,
Hosokawa Hiroyuki,
Hasegawa Akihiro,
Watarai Hiroshi,
Taniguchi Masaru,
Yamashita Masakatsu,
Nakayama Toshinori
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02854.x
Subject(s) - enhancer , function (biology) , biology , microbiology and biotechnology , immunology , genetics , transcription factor , gene
Summary GATA‐3 is the master transcription factor for T helper 2 (Th2) cell differentiation and is critical for the expression of Th2 cytokines. Little is known, however, about the nature of the functional molecular complexes of GATA‐3. We identified a high‐mobility group (HMG)‐box type transcription factor, lymphoid enhancer factor 1 (LEF‐1), in the GATA‐3 complex present in Th2 cells using a Flag‐calmodulin‐binding peptide (CBP)‐tag based proteomics method. The interaction between GATA‐3 and LEF‐1 was confirmed by co‐immunoprecipitation experiments using LEF‐1‐introduced T‐cell lineage TG40 cells. The HMG‐box domain of LEF‐1 and two zinc finger domains of GATA‐3 were found to be important for the physical association. The introduction of LEF‐1 into developing Th2 cells resulted in the suppression of Th2 cytokine production. The suppression was significantly lower in the cells into which a HMG‐box‐deleted LEF‐1 mutant was introduced. Moreover, LEF‐1 inhibited the binding activity of GATA‐3 to the interleukin (IL)‐5 promoter. These results suggest that LEF‐1 is involved in the GATA‐3 complex, while also regulating the GATA‐3 function, such as the induction of Th2 cytokine expression via the inhibition of the DNA‐binding activity of GATA‐3.