HDAC4 inhibits the transcriptional activation of mda-7/IL-24 induced by Sp1.
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.
Pan
Lina
L
Institute of Genetics and Cytology, Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China.
Pan
Hong
H
Jiang
Hao
H
Du
Juan
J
Wang
Xiuli
X
Huang
Baiqu
B
Lu
Jun
J
D000107:Acetylation; D045744:Cell Line, Tumor; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics*; D011485:Protein Binding; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects; D000099180:Interleukin-24
D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D007378:Interleukins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D000099180:Interleukin-24; C012589:trichostatin A; C400300:HDAC4 protein, human
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