摘要
Melanoma differentiation-associated gene/interleukin-24(mda-7/IL-24)is a cytokine that can activate monocytes and T helper 2 cells.The expression of mda-7/IL-24 gradually fades with the progression of melanoma,and it is undetectable at the metastatic stage.Ectopic expression of mda-7/IL-24 selectively suppresses growth and induces apoptosis in cancer cells with little harm to normal cells.However,the transcriptional regulation of the mda-7/IL-24 gene has not been extensively studied.In this study,we show that the expression of mda-7/IL-24 was upregulated by the histone deacetylase(HDAC)inhibitors trichostatin A(TSA)and sodium butyrate(NaBu),whereas it was downregulated by HDAC4.We also found that the histone acetylation level and the binding of the transcriptional factor Sp1 to the mad-7 promoter were reduced upon HDAC4 treatment.Moreover,the HDAC inhibitor TSA induced histone hyperacetylation and stimulated Sp1 binding to the mda-7/IL-24 promoter,which in turn enhanced the expression of mda-7/IL-24.Therefore,we conclude that histone acetylation modification plays an important role in the regulation of mda-7/IL-24 and that the transcription factor Sp1 participates in this process.
基金
This work was supported by grants from the National Natural Science Foundation of China(No.30671184)
the Program for Changjiang Scholars and Innovative Research Team in University(No.IRT0519).
