Type 10 17β-hydroxysteroid dehydrogenase expression is regulated by C/EBPβ in HepG2 cells.
17β-hydroxysteroid dehydrogenases (HSD17Bs) are enzymes that stereospecifically reduce or oxidize a keto- or hydroxy group at C17 of the steroid scaffold, respectively. Fourteen mammalian HSD17Bs have been identified so far. We previously described that the HSD17B8 gene is regulated by C/EBPβ in the hepatocarcinoma cell line HepG2. Here, we analyze the 5'-flanking region of 14 promoters (HSD17B1-14) looking for CCAAT boxes and binding sites for CCAAT enhancer binding factors (C/EBPs). All promoters were found to have binding sites for these transcription factors except HSD17B1. Ectopic expression of C/EBPα or C/EBPβ in HepG2 cells showed that HSD17B11 expression was induced by both transcription factors while HSD17B10 expression was only induced by C/EBPβ. The first 500bp of the 5'-flanking region of both genes contain two putative binding sites for C/EBPs. Gene reporter assays showed that C/EBPβ transactivated HSD17B10 but not HSD17B11. Additional experiments showed that several isoforms of C/EBPβ are involved in HSD17B10 regulation. Mutation of the CCAAT box located at -30/-19 induced HSD17B10 promoter activity when only LIP was expressed, while impaired LAP-induced HSD17B10 transactivation in HepG2 cells when LAP isoforms are expressed. Taken together, our findings reveal that HSD17B10 is regulated by several isoforms of C/EBPβ in HepG2 cells.
Rotinen
Mirja
M
Department of Health Sciences, Universidad Pública de Navarra, Avda Barañain, 31008 Pamplona, Spain.
Villar
Joaquín
J
Celay
Jon
J
Encío
Ignacio
I
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics*; D001483:Base Sequence; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015533:Transcriptional Activation
D022782:CCAAT-Enhancer-Binding Protein-beta; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human