Cited 29 times in
Differential regulation of human and mouse orphan nuclear receptor small heterodimer partner promoter by sterol regulatory element binding protein-1
DC Field | Value | Language |
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dc.contributor.author | 김경섭 | - |
dc.date.accessioned | 2015-07-14T17:13:59Z | - |
dc.date.available | 2015-07-14T17:13:59Z | - |
dc.date.issued | 2004 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/112470 | - |
dc.description.abstract | Small heterodimer partner (SHP; NR0B2) is an unusual orphan nuclear receptor that lacks a conventional DNA-binding domain and acts as a modulator of transcriptional activities of a number of nuclear receptors. Herein, we report that the human SHP promoter (hSHP) is activated by sterol regulatory element-binding protein-1 (SREBP-1), which regulates the expression of various genes involved in cholesterol and fatty acid synthesis. Overexpression of SREBP-1 activated the human but not mouse SHP promoter, although SREBP-2 had little effect on the SHP promoter in CV-1 cells. Serial deletion reporter assays revealed that SREBP-1-responsive region is located within the sequences from -243 to -120 bp in the hSHP promoter. DNase I footprinting, gel shift assays, and chromatin immunoprecipitation assays demonstrated that SREBP-1 binds directly to the hSHP promoter. Site-directed mutagenesis made it clear that the hSHP promoter activation by SREBP-1 is mostly mediated by the SRE1 (-186 to -195 bp) in the hSHP promoter, which is not conserved in the mouse SHP promoter. Moreover, adenovirus-mediated overexpression of SREBP-1c/ADD-1 induced SHP mRNA expression and repressed CYP7A1 expression in HepG2 cells. Finally, we found that a four-nucleotide deletion (-195CT-GAdel) in the hSHP promoter, which is reported to be associated with altered body weight and insulin secretion in human, coincides with the SRE1. This mutation strongly decreased both basal and SREBP-1 dependent activities of the hSHP promoter, because of the reduced binding of SREBP-1 to the mutated SRE1. Overall, our results demonstrate a differential regulation of human and mouse SHP promoters by SREBP-1. We propose a possible role of SREBP-1 in the species differential regulation of cholesterol and bile acid homeostasis via a novel mechanism of up-regulation of the hSHP gene expression. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 28122~28131 | - |
dc.relation.isPartOf | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Differential regulation of human and mouse orphan nuclear receptor small heterodimer partner promoter by sterol regulatory element binding protein-1 | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Biochemistry & Molecular Biology (생화학,분자생물학) | - |
dc.contributor.googleauthor | Han-Jong Kim | - |
dc.contributor.googleauthor | Joon-Young Kim | - |
dc.contributor.googleauthor | Hueng-Sik Choi | - |
dc.contributor.googleauthor | Kyung-Sup Kim | - |
dc.contributor.googleauthor | In-Kyu Lee | - |
dc.contributor.googleauthor | Jae Bum Kim | - |
dc.contributor.googleauthor | Ji-Ho Seo | - |
dc.contributor.googleauthor | Sang-Kyu Park | - |
dc.contributor.googleauthor | Ju-Youn Kim | - |
dc.identifier.doi | 10.1074/jbc.M313302200 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.relation.journalcode | J01258 | - |
dc.identifier.eissn | 1083-351X | - |
dc.contributor.alternativeName | Kim, Kyung Sup | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 279 | - |
dc.citation.number | 27 | - |
dc.citation.startPage | 28122 | - |
dc.citation.endPage | 28131 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.279(27) : 28122-28131, 2004 | - |
dc.identifier.rimsid | 56194 | - |
dc.type.rims | ART | - |
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