Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells.
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.
Hossain
Mohammad B
MB
Department of Immunology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
Hosokawa
Hiroyuki
H
Hasegawa
Akihiro
A
Watarai
Hiroshi
H
Taniguchi
Masaru
M
Yamashita
Masakatsu
M
Nakayama
Toshinori
T
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D024742:HMG-Box Domains / Q000276:immunology; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D018418:Th2 Cells / Q000276:immunology*; D016335:Zinc Fingers / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D051821:Lymphoid Enhancer-Binding Factor 1