Synergistic regulation of hepatic Fsp27b expression by HNF4? and CREBH.

ABSTRACT: 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 4? (HNF4?) has an important role in lipid homeostasis because liver-specific HNF4?-null mice (Hnf4a?Hep mice) exhibit hepatosteatosis. We investigated whether HNF4? directly regulates expression of CIDE family genes. Expression of Cideb and Fsp27b was largely decreased in Hnf4a?Hep 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 HNF4? expression was knocked down. Conversely, overexpression of HNF4? strongly induced CIDEC2 expression in hepatoma cell lines. Furthermore, HNF4? transactivated Fsp27b by direct binding to an HNF4? response element in the Fsp27b promoter. In addition, Fsp27b is known to be transactivated by CREBH that is regulated by HNF4?, and expression of CREBH was induced by HNF4? in human hepatoma cells. Co-transfection of HNF4? and CREBH resulted in synergistic transactivation and induction of Fsp27b compared to that of HNF4? or CREBH alone. These results suggest that HNF4?, in conjunction with CREBH, plays an important role in regulation of Fsp27b expression.

SUBMITTER: Kasano-Camones CI 

PROVIDER: S-EPMC7484291 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature