HDAC4 inhibits the transcriptional activation of mda-7/IL-24 induced by Sp1

被引:0
作者
Lina Pan
Hong Pan
Hao Jiang
Juan Du
Xiuli Wang
Baiqu Huang
Jun Lu
机构
[1] Institute of Genetics and Cytology,
[2] Key Laboratory of Molecular Epigenetics of the Ministry of Education,undefined
[3] Northeast Normal University,undefined
[4] College of Chemistry and Life Science,undefined
[5] Tianjin Key Laboratory of Cyto-Genetical and Molecular Regulation,undefined
[6] Tianjin Normal University,undefined
来源
Cellular & Molecular Immunology | 2010年 / 7卷
关键词
HDAC4; HDAC inhibitors; histone acetylation; mda-7/IL-24; Sp1;
D O I
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学科分类号
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.
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页码:221 / 226
页数:5
相关论文
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