FAM3A is a target gene of peroxisome proliferator-activated receptor gamma

• Published in: Biochimica et biophysica acta Vol. 1830; no. 8; pp. 4160 - 4170
• Main Authors: Zhou, Yanlan, Jia, Shi, Wang, Chunjiong, Chen, Zhenzhen, Chi, Yujing, Li, Jing, Xu, Guoheng, Guan, Youfei, Yang, Jichun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2013
• Subjects: agonists; Akt; Animals; Base Sequence; Cells, Cultured; chromatin; Cytokines - genetics; FAM3A; genes; Hep G2 Cells; hepatocytes; human cell lines; Humans; liver; Liver - metabolism; luciferase; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Nuclear receptor; Palmitates - pharmacology; PPAR gamma - physiology; PPARγ; PPRE; precipitin tests; promoter regions; Promoter Regions, Genetic; receptors; site-directed mutagenesis; Thiazolidinediones - pharmacology; transcription (genetics); transcription factors; FAM3A; Nuclear receptor; Akt; PPRE; PPARγ
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.03.029

To date, the biological function of FAM3A, the first member of FAM3 gene family, remains unknown. We aimed to investigate whether the expression of FAM3A in liver cells is regulated by peroxisome proliferator-activated receptors (PPARs). The transcriptional activity of human and mouse FAM3A gene promoters was determined by luciferase reporter assay system. PPARγ agonist rosiglitazone induced FAM3A expression in primary cultured mouse hepatocytes and human HepG2 cells. PPARγ antagonism blocked rosiglitazone-induced FAM3A expression, whereas PPARγ overexpression stimulated FAM3A expression in HepG2 cells. In contrast, PPARα agonist fenofibrate or PPARβ agonist GW0742 failed to affect FAM3A expression in HepG2 cells. The transcriptional activities of human and mouse FAM3A promoters were markedly stimulated by PPARγ activation, but not by PPARα and PPARβ activation. Chromatin immunoprecipitation (ChIP) assay revealed a direct binding of PPARγ to the putative peroxisome proliferator response element (PPRE) located at −1258/−1246 in the human FAM3A promoter. Site-directed mutagenesis of this PPRE-like motif abolished PPARγ's stimulatory effect on the transcriptional activity of human FAM3A promoter. In vivo, oral rosiglitazone treatment upregulated FAM3A expression in the livers of C57BL/6 mice and db/db mice. Moreover, upregulation of FAM3A by PPARγ activation was correlated with increased level of phosphorylated Akt (pAkt) in liver cells. FAM3A as a novel target gene of PPARγ. Upregulation of FAM3A by PPARγ activation is correlated with increased pAkt level in liver cells. Upregulation of FAM3A might contribute to PPARγ's metabolic effects in the liver. •PARγ activation induces FAM3A expression in HepG2 cells, primary cultured mouse hepatocytes and mouse livers.•The mouse and human FAM3A genes are the target gene of PPARγ.•Upregulation of FAM3A by PPARγ activation is correlated with increased level of phosphorylated Akt in liver cells.