The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Characterization of the Human PPARα Promoter: Identification of a Functional Nuclear Receptor Response Element
Open accessAbstract
PPARalpha is a nuclear receptor that controls lipid and glucose metabolism and exerts antiinflammatory activities. The factors regulating human PPARalpha (hPPARalpha) gene expression remain largely unexplored. To study the mechanisms controlling hPPARalpha expression, the hPPARalpha gene promoter was identified and characterized. First, an alternatively spliced exon within the 5'-untranslated region of the hPPARalpha gene was identified by RT-PCR. Next, the transcription start site was mapped and the hPPARalpha gene promoter was cloned and functionally analyzed. Because PPARalpha levels are elevated in tissues expressing the hepatocyte nuclear factor-4 (HNF4), such as liver, the regulation of hPPARalpha by HNF4 was examined. Transient transfections in HepG2 and Cos cells showed that HNF4 enhances hPPARalpha promoter activity. 5'-Deletion and mutation analysis of the hPPARalpha promoter identified a regulatory element (RE) consisting of a degenerate hexamer repeat with a single nucleotide spacer (direct repeat 1), termed alphaHNF4-RE. Gel shift assays demonstrated that HNF4 binds to this alphaHNF4-RE. Furthermore, HNF4 increased the activity of a heterologous promoter driven by two copies of the alphaHNF4-RE. The nuclear receptor COUP-TFII also bound this site and down-regulated basal as well as HNF4-induced hPPARalpha promoter activity. Finally, PPARalpha was shown to bind the alphaHNF4-RE, leading to an induction of PPARalpha expression in hepatocytes. In summary, the organization of the 5'-flanking and untranslated region of the hPPARalpha gene was characterized and the hPPARalpha promoter region has been identified. Furthermore, these data demonstrate that the hPPARalpha gene is regulated by nuclear receptors, such as HNF-4, COUP-TFII, and PPARalpha.
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The PPARs: From Orphan Receptors to Drug Discovery
Willson, T. M., Brown, P. J., Sternbach, D. D., & Henke, B. R. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990554g · Cited by 1,816
Mechanism of Action of Fibrates on Lipid and Lipoprotein Metabolism
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Self-citationChinetti, G., Lestavel, S., Bocher, V., Remaley, A. T., Neve, B., Torra, I. P., Teissier, E., Minnich, A., Jaye, M., Duverger, N., et al. (2001) · Nature Medicine · doi:10.1038/83348 · Cited by 1,170
Self-citationHayhurst, G. P., Lee, Y.-H., Lambert, G., Ward, J. M., & Gonzalez, F. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.4.1393-1403.2001 · Cited by 1,107
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Self-citationGuerre-Millo, M., Gervois, P., Raspé, E., Madsen, L., Poulain, P., Derudas, B., Herbert, J.-M., Winegar, D. A., Willson, T. M., Fruchart, J.-C., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.22.16638 · Cited by 605
Self-citationStaels, B., Vu-Dac, N., Kosykh, V. A., Saladin, R., Fruchart, J. C., Dallongeville, J., & Auwerx, J. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117717 · Cited by 410
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Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Lefebvre, P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27989 · Cited by 962
Molecular Actions of PPARα in Lipid Metabolism and Inflammation
Bougarne, N., Weyers, B., Desmet, S. J., Deckers, J., Ray, D. W., Staels, B., & De Bosscher, K. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00064 · Cited by 898
Self-citationTranscriptional Regulation of Metabolism
Desvergne, B., Michalik, L., & Wahli, W. (2006) · Physiological Reviews · doi:10.1152/physrev.00025.2005 · Cited by 892
Lipin 1 is an inducible amplifier of the hepatic PGC-1α/PPARα regulatory pathway
Finck, B. N., Gropler, M. C., Chen, Z., Leone, T. C., Croce, M. A., Harris, T. E., Lawrence, J. C., & Kelly, D. P. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.08.005 · Cited by 554
Huss, J. M., Torra, I. P., Staels, B., Giguère, V., & Kelly, D. P. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.20.9079-9091.2004 · Cited by 485
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Metadata
- Authors
- Pineda Torra, I., Jamshidi, Y., Flavell, D. M., Fruchart, J.-C., & Staels, B.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2002-05
- Volume
- 16
- Issue
- 5
- Pages
- 1013-1028
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2124317382
- Cited by
- 164
- References
- 9
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- bronze
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