SREBP-2 and NF-Y are involved in the transcriptional regulation of squalene epoxidase.
The expression of squalene epoxidase (SE) is highly regulated transcriptionally by cholesterol. To elucidate these molecular mechanisms, we isolated the human and rat genomic clones. The entire human SE gene was about 24 kb long and organized into 11 exons with 10 introns. Unidirectional deletion analysis of the human 5(')-flanking region indicated that the sequence between -264 and -230 bp conferred cholesterol sensitivity on a reporter gene. This region contained a potential copy of consensus sterol regulatory element (SRE) sequence (CCACGCAAC) previously identified in the promoter of cholesterogenic and its related genes. The transcriptional activation observed under overexpression of sterol regulatory element binding protein-2 (SREBP-2) supported the functional role of the SRE sequence. Another deletion analysis showed that the sequence -207 to -192 bp was also active and it contained nuclear factor Y (NF-Y) binding site. Both sites might play critical roles in sterol mediated regulation of SE gene.
Nagai
Masaaki
M
Department of Biochemistry and Internal Medicine, Niigata University School of Medicine, 1-757 Asahimachidori, Niigata 951-8510, Japan. mnagai@ucsd.edu
Sakakibara
Jun
J
Nakamura
Yuichi
Y
Gejyo
Fumitake
F
Ono
Teruo
T
D024506:5' Flanking Region; D000818:Animals; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000502:physiology*; D002784:Cholesterol / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D010105:Oxygenases / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats; D020218:Response Elements; D016415:Sequence Alignment; D050603:Squalene Monooxygenase; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
D023081:CCAAT-Binding Factor; D004268:DNA-Binding Proteins; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D002784:Cholesterol; D010105:Oxygenases; D050603:Squalene Monooxygenase