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Histone Acetylation Enhances the Transcriptional Activation of Mda-7 Induced by Sp1

Author: PanHong
Tutor: HuangBaiQu
School: Northeast Normal University
Course: Cell Biology
Keywords: HDAC4 HDAC inhibitors Histone acetylation mda-7 Sp1
CLC: R739.5
Type: Master's thesis
Year: 2011
Downloads: 12
Quote: 0
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Abstract


Mda-7/IL-24 ( melanoma differentiation associated gene / interleukin -24 ) was first discovered as a cytokine , in human peripheral blood mononuclear cells (PBMC) PHA or LPS-induced expression . Mda-7 gene is located on IL - 10 gene in the gene cluster is a Th1 cell -promoting factor . Adenovirus -mediated mda-7 to promote IL - 6 and IFN-γ expression , and induction of melanoma cells to secrete IFN-γ and IL - 6 . In addition , mda-7 is also a tumor suppressor gene is constitutively expressed in normal melanocytes , in order to maintain normal physiological functions of the cells , and induction of cell terminal differentiation . With the process of melanoma , and its expression is gradually reduced , substantially undetectable in the transfer stage . Adenovirus -mediated mda-7 ectopic expression can selectively induce apoptosis in a wide range of tumor cells and normal cells with minimal side effects . Furthermore, there is evidence that the lack of expression of the mda-7 is not a gene mutation results in the tumor cells , contrast , cancer cells and normal cells found no changes in gene structure . Cancer mda-7 can be induced to express the fact that there may be other mechanisms for regulation of mda - 7 expression . Presumably, such as epigenetic changes in histone acetylation modification in the regulation of expression of mda-7 may play a role , but no related research reports . In the present study , we demonstrated that the histone deacetylase inhibitor TSA and the NaBu able to activate the expression of mda-7 , histone deacetylase 4 (HDAC4) can be partially reversed this role . Also found that HDAC4 overexpression of mda-7 promoter at reduced levels of histone acetylation and inhibition of the combination of the transcription factor Sp1 mda-7 promoter . In addition , the histone deacetylase inhibitor TSA induced histone hyperacetylated promote Sp1 mda-7 promoter binding , thereby activating the expression of mda-7 . Therefore , we have come to the conclusion histone acetylation play an important role in the regulation of expression of mda-7 , and the transcription factor Sp1 involved in this process .

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