Transcriptional regulation of the apolipoprotein F (ApoF) gene by ETS and C/EBPα in hepatoma cells.
Apolipoprotein F (ApoF) inhibits cholesteryl ester transfer protein (CETP) activity and plays an important role in lipid metabolism. In the present study, the full-length human ApoF promoter was cloned, and the molecular mechanism of the regulation of ApoF was investigated. The ApoF promoter displayed higher activities in hepatoma cell lines, and the -198 nt to +79 nt promoter region contained the maximum promoter activity. In the promoter region of -198 nt to -2 nt there were four putative binding sites for transcription factors ETS-1/ETS-2 (named EBS-1 to EBS-4) and one for C/EBP. Mutation of EBS-2, EBS4 and the C/EBP binding site abolished the promoter activity, and ETS-1/ETS-2 and C/EBPα could interact with corresponding binding sites. In addition, overexpression of ETS-1/2 or C/EBPα enhanced, while dominant-negative mutants of ETS-1/2 and knockdown of C/EBPα decreased, ApoF promoter activities. ETS-1 and C/EBPα associated physically, and acted synergistically to activate ApoF transcription. These results demonstrated combined activation of the ApoF promoter by liver-enriched and ubiquitous transcription factors. Direct interactions between C/EBPα and ETS-1 were important for high liver-specific expression of ApoF.
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Department of Cardiology, Affiliated Nanping First Hospital, Fujian Medical University, Nanping, China.
Xue-Bin
XB
Shen
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Department of Cardiology, Affiliated Nanping First Hospital, Fujian Medical University, Nanping, China.
Ling
L
Huang
Department of Medical Laboratory, Affiliated Nanping First Hospital, Fujian Medical University, Nanping, China.
Shao-Hong
SH
Zhang
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Department of Endocrinology and Metabolism, Hongqi Hospital of MuDanJiang Medical College, Mudanjiang, China.
De-Ping
DP
Wang
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Yun-Li
YL
Wu
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Wan-Nan
WN
Chen
Department of Cardiology, Affiliated Nanping First Hospital, Fujian Medical University, Nanping, China. Electronic address: 18905990816@163.com.
Shang-Hua
SH
Xu
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China. Electronic address: linxu@mail.fjmu.edu.cn.
Xu
X
Lin
D001053:Apolipoproteins / Q000096:biosynthesis* / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D014158:Transcription, Genetic
D001053:Apolipoproteins; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C494041:ETS1 protein, human; C494069:ETS2 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; C036321:apolipoprotein F
Apolipoprotein F; CCAAT/enhancer binding protein; E-twenty-six; Lipid transfer inhibitor protein; Promoter