A simple promoter containing two Sp1 sites controls the expression of sterol-regulatory-element-binding protein 1a (SREBP-1a).
The mammalian gene for SREBP-1 (sterol-regulatory-element-binding protein 1) contains two promoters that control the production of two proteins, SREBP-1a and -1c, and each contains a unique N-terminal transcriptional activation domain, but they are otherwise identical. The relative level of each mRNA varies from tissue to tissue and they respond differently to regulatory stimuli. SREBP-1c is more abundantly expressed in liver, where its level is also regulated by insulin and liver X receptor activators, and it is also autoregulated by SREBPs. In contrast, SREBP-1a mRNA levels are relatively low and constant in different tissues and few studies have specifically analysed its pattern of expression and regulation. In the present study, we show that the promoter for SREBP-1a is contained in a very small promoter-proximal region containing two Sp1 sites. The small and relatively simple structure for its promoter provides an explanation for the low level of SREBP-1a expression. Additionally, since Sp1 has been implicated in the modest regulation of several genes by insulin, its involvement in the expression of the SREBP-1a promoter provides an explanation for the modest insulin regulation observed in animal experiments.
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA.
Chengkang
C
Zhang
Dong-Ju
DJ
Shin
Timothy F
TF
Osborne
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004331:Drosophila melanogaster / Q000166:cytology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013045:Species Specificity; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D020033:Protein Isoforms; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D016329:Sp1 Transcription Factor; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors