Sterol-mediated regulation of human lipin 1 gene expression in hepatoblastoma cells.
Lipin 1 plays a crucial role in lipid metabolism in adipose tissue, skeletal muscle, and liver. Its physiological role involves two cellular functions: regulation of phosphatidate phosphatase activity and regulation of fatty acid oxidation. In this study, we have demonstrated that lipin 1 gene (LPIN1) expression is regulated by cellular sterols, which are key regulators of lipid metabolism. We have also characterized the sterol-response element and nuclear factor Y-binding sites in the human LPIN1 promoter. Using a luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, we demonstrated that these elements are responsible for the transcription of LPIN1 gene, mediated by SREBP-1 (sterol regulatory element-binding protein 1) and nuclear factor Y. Furthermore, we investigated whether lipin 1 is involved in lipogenesis by transfection of LPIN1 small interfering RNA. We infer that sterol-mediated regulation of lipin 1 gene transcription modulates triglyceride accumulation. This modulation involves changes in the activity of phosphatidate phosphatase.
Ishimoto
Kenji
K
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871; Department of Molecular Pharmaceutical Science, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871.
Nakamura
Hiroki
H
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871.
Tachibana
Keisuke
K
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871.
Yamasaki
Daisuke
D
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871.
Ota
Akemi
A
Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871.
Hirano
Ken-Ichi
KI
Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871.
Tanaka
Toshiya
T
Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan.
Hamakubo
Takao
T
Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan.
Sakai
Juro
J
Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan.
Kodama
Tatsuhiko
T
Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan.
Doi
Takefumi
T
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871; Department of Molecular Pharmaceutical Science, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871.
D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018197:Hepatoblastoma / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010711:Phosphatidate Phosphatase; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D020218:Response Elements; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D013261:Sterols / Q000378:metabolism*; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism
D023081:CCAAT-Binding Factor; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D013261:Sterols; D014280:Triglycerides; C402244:nuclear factor Y; C485999:LPIN1 protein, human; D010711:Phosphatidate Phosphatase