TAILIEUCHUNG - Báo cáo khoa học: Alpha 1-antichymotrypsin/SerpinA3 is a novel target of orphan nuclear receptor Nur77

Nur77 is one member of the nuclear receptor superfamily. As a transcrip-tion factor, Nur77 participates in a variety of biological processes, includ-ing T cell development, inflammatory responses, steroid hormone synthesis, and hepatic glucose metabolism. It typically acts via binding to the Nur77 responsive element (NBRE) in the promoter regions of its target genes. | ỊFEBS Journal Alpha 1-antichymotrypsin SerpinA3 is a novel target of orphan nuclear receptor Nur77 Yongjuan Zhao Yanxin Liu and Dexian Zheng State Key Laboratory of MedicalMolecular Biology Institute of Basic MedicalSciences Chinese Academy of MedicalSciences Peking Union MedicalCollege Beijing China Keywords gene regulation genome-wide scan NBRE Nur77 transcription factor SerpinA3 Correspondence D. Zheng Institute of Basic Medical Sciences 5 Dong Dan San Tiao Beijing 100005 China Fax 86 10 6510 5102 Tel 86 10 6529 6409 E-mail zhengdx@ or zhengdx@ Received 17 September 2007 revised 27 December 2007 accepted 3 January 2008 doi Nur77 is one member of the nuclear receptor superfamily. As a transcription factor Nur77 participates in a variety of biological processes including T cell development inflammatory responses steroid hormone synthesis and hepatic glucose metabolism. It typically acts via binding to the Nur77 responsive element NBRE in the promoter regions of its target genes. In the present study we identified a novel Nur77-regulated gene a1-anti-chymotrypsin SerpinA3 via an approach combining computational prediction and wet-laboratory validations. First we identified 483 candidate genes via a human genome-wide scan for NBREs in their proximal promoters. Three out of 14 function-associated genes were further identified to be transactivated by Nur77 in luciferase reporter gene assays in HEK 293T cells. The transactivation assay proved that the NBRE -182 to -175 in the SerpinA3 promoter region is a novel Nur77-dependent functional motif in HEK 293T and HepG2 cells. Electrophoretic mobility shift and chromatin immunoprecipitation assays demonstrated that Nur77 physically associates with the SerpinA3 promoter region both in vitro and in vivo. Nur77 overexpression and RNA interference-mediated Nur77 gene knockdown analysis confirmed that SerpinA3 is indeed a novel Nur77-targeted gene. These data may throw light on

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