Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells
Article first published online: 28 APR 2008
© 2008 The Authors Journal compilation © 2008 Blackwell Publishing Ltd
Volume 125, Issue 3, pages 377–386, November 2008
How to Cite
Hossain, M. B., Hosokawa, H., Hasegawa, A., Watarai, H., Taniguchi, M., Yamashita, M. and Nakayama, T. (2008), Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells. Immunology, 125: 377–386. doi: 10.1111/j.1365-2567.2008.02854.x
- Issue published online: 8 OCT 2008
- Article first published online: 28 APR 2008
- Received 11 January 2008; revised 18, 21 March 2008; accepted 27 March 2008.
- HMG box;
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.