Analysis of the 5' flanking regions of human and murine HSD17B7: identification of a cholesterol dependent enhancer region.
17Beta hydroxysteroid dehydrogenase type 7 (HSD17B7) was described to possess dual functionality in steroidogenesis as well as in postsqualene cholesterol biosynthesis in vitro. In order to gain insight into the transcriptional regulation, and thereby into in vivo functionality of HSD17B7, we analyzed and compared the 5' flanking regions of the corresponding human and murine genes. For this task we used bioinformatic and experimental approaches. The identified proximal promoter regions of both human and murine HSD17B7 genes contain multiple transcription factor binding sites and show strong similarity to cholesterogenic genes, especially to other postsqualene genes, but not to other steroidogenic genes. In liver cell lines, the transcriptional activity is dependent on the level of cholesterol, but not estradiol. The results of our study lead us to the conclusion that HSD17B7 is involved in postsqualene cholesterol biosynthesis in both human and mice.
Ohnesorg
Thomas
T
GSF-National Research Center for Environment and Health, Institute of Experimental Genetics, Genome Analysis Center, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
Adamski
Jerzy
J
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D024506:5' Flanking Region / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis* / Q000494:pharmacology; D019295:Computational Biology; D004742:Enhancer Elements, Genetic; D004958:Estradiol / Q000494:pharmacology; D005796:Genes; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects
D004958:Estradiol; D002784:Cholesterol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase