Anakysis of GATA-3 function in proliferation and differentiation of kerationocytes

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In epidermal keratinocytes, we demonstrated that GATA-3 was more abundant in differentiated keratinocytes than undifferentiated keratinocytes, suggesting that GATA-3 might contribute to differntiatioirspecific gene regulation. We previously showed that c-Fos and Sp1 activate the loricrin promoter activity in differentiated keratinocytes while c-Jun and Sp3 suppress it in undifferentiated keratinocytes. Thus, we tested the cooperative tarnsactivation of loricrin promoter activity by GATA-3, c-Fos and Sp1. Transactivation experiments presented here provide evidence that GATA-3, c-Fos and Sp1 can activate the loricrin promoter transcription in a synergistic manner even though the GATA-3 binding motif is deleted from the promoter. These results strongly suggest the interaction among those proteins. Thus, we examined the physical binding among GATA-3, AP-1 and Sp1/Sp3. In vitro binding by means of a glutathione S-transferase pull down assay showed that c-Jun/c-Fos could directly associate with GATA-3. However, binding affinity of GATA-3 with Sp1 was much less than that with c-Fos, These results suggest that GATA-3 can interact with c-Fos directly while GATA-3 may interact with Sp1 via other transcription factors or cofactors.