First Author | Kasano-Camones CI | Year | 2020 |
Journal | Biochem Biophys Res Commun | Volume | 530 |
Issue | 2 | Pages | 432-439 |
PubMed ID | 32553626 | Mgi Jnum | J:304217 |
Mgi Id | MGI:6694425 | Doi | 10.1016/j.bbrc.2020.05.070 |
Citation | Kasano-Camones CI, et al. (2020) Synergistic regulation of hepatic Fsp27b expression by HNF4alpha and CREBH. Biochem Biophys Res Commun 530(2):432-439 |
abstractText | The CIDE (cell death-inducing DFF45-like effector) family composed of CIDEA, CIDEB, CIDEC/FSP27 (fat-specific protein 27), has a critical role in growth of lipid droplets. Of these, CIDEB and CIDEC2/FSP27B are abundant in the liver, and the steatotic livers, respectively. Hepatocyte nuclear factor 4alpha (HNF4alpha) has an important role in lipid homeostasis because liver-specific HNF4alpha-null mice (Hnf4a(DeltaHep) mice) exhibit hepatosteatosis. We investigated whether HNF4alpha directly regulates expression of CIDE family genes. Expression of Cideb and Fsp27b was largely decreased in Hnf4a(DeltaHep) mice, while expression of Cidea was increased. Similar results were observed only in CIDEC2, the human orthologue of the Fsp27b, in human hepatoma cell lines in which HNF4alpha expression was knocked down. Conversely, overexpression of HNF4alpha strongly induced CIDEC2 expression in hepatoma cell lines. Furthermore, HNF4alpha transactivated Fsp27b by direct binding to an HNF4alpha response element in the Fsp27b promoter. In addition, Fsp27b is known to be transactivated by CREBH that is regulated by HNF4alpha, and expression of CREBH was induced by HNF4alpha in human hepatoma cells. Co-transfection of HNF4alpha and CREBH resulted in synergistic transactivation and induction of Fsp27b compared to that of HNF4alpha or CREBH alone. These results suggest that HNF4alpha, in conjunction with CREBH, plays an important role in regulation of Fsp27b expression. |