title: Regulation of DEK expression by AP-2α and methylation level of DEK promoter in hepatocellular carcinoma.
abstract: DEK is overexpressed in multiple invasive tumors. However, the transcriptional regulatory mechanism of DEK remains unclear. In the present study, progressive-type truncation assay indicated that CpG2-2 (-167 bp/+35 bp) was the DEK core promoter, whose methylation inhibited DEK expression. Bisulfite genomic sequencing analysis indicated that the methylation levels of the DEK promoter in normal hepatic cells and tissues were higher than those in hepatocellular carcinoma (HCC) cells. TFSEARCH result revealed transcription factor binding sites in CpG2-2. Among the sites, the AP-2α binding site showed the most significant methylation difference; hence, AP-2α is a key transcription factor that regulates DEK expression. Point or deletion mutation of the AP-2α binding site significantly reduced the promoter activity. Chromatin immunoprecipitation assay demonstrated the binding of AP-2α to the core promoter. Furthermore, knock down of endogenous AP-2α downregulated DEK expression, whereas overexpression of AP-2α upregulated DEK expression. Thus, AP-2α is an important transcription factor of DEK expression, which is correlated with the methylation level of the DEK core promoter in HCC.
authors: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing 100044, P.R. China.
authors: Ming-Xu
authors: MX
authors: Qiao
authors: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing 100044, P.R. China.
authors: Chun
authors: C
authors: Li
authors: Institute of Hepatobiliary Surgery, PLA General Hospital, Beijing 100853, P.R. China.
authors: Ai-Qun
authors: AQ
authors: Zhang
authors: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing 100044, P.R. China.
authors: Ling-Ling
authors: LL
authors: Hou
authors: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing 100044, P.R. China.
authors: Juan
authors: J
authors: Yang
authors: College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing 100044, P.R. China.
authors: Hong-Gang
authors: HG
authors: Hu
mesh_terms: D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D050656:Transcription Factor AP-2 / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C084738:DEK protein, human; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D050656:Transcription Factor AP-2