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短篇通讯:牛固醇调节元件结合蛋白-1c 启动子的鉴定及其被肝 X 受体激活。

Short communication: Identification of the bovine sterol regulatory element binding protein-1c promoter and its activation by liver X receptor.

机构信息

Department of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg 24061-0315, USA.

出版信息

J Dairy Sci. 2010 Dec;93(12):5831-6. doi: 10.3168/jds.2010-3236.

Abstract

Sterol regulatory element binding proteins (SREBP) are a family of transcription factors that regulate cholesterogenesis and lipogenesis. Sterol regulatory element binding proteins-1a and -1c are transcribed from the same gene by the use of alternate promoters, and only differ at their first exon. Sterol regulatory element binding protein-1c is hypothesized to be an important regulator of genes involved in milk fat synthesis in the lactating dairy cow. However, the bovine SREBP-1c promoter has not been previously characterized, and studies to date that have investigated the role of SREBP-1 in the bovine mammary gland have not distinguished between isoforms 1a and 1c. The purpose of this study was to characterize the bovine SREBP-1c promoter and to investigate the DNA elements involved in the regulation of SREBP-1c expression by the liver X receptor agonist T0901317 in 2 different bovine mammary epithelial cell lines. Luciferase reporter constructs containing the wild-type SREBP-1c promoter or constructs with mutated liver X receptor response elements or sterol response element were transfected into MacT cells and bovine mammary epithelial (BME-UV) cells. We have demonstrated that the liver X receptor response elements sites in the SREBP-1c promoter are necessary for mediating the T0901317 response, and that stimulation through the sterol response element site plays only a minor role in this pathway. This report describes the bovine SREBP-1c promoter and its regulation by liver X receptor in bovine mammary epithelial cells.

摘要

固醇调节元件结合蛋白(SREBP)是一类调节胆固醇和脂肪生成的转录因子。SREBP-1a 和 SREBP-1c 由同一个基因通过不同启动子转录而成,仅在其第一外显子上有所不同。SREBP-1c 被认为是泌乳奶牛乳脂合成相关基因的重要调节因子。然而,牛 SREBP-1c 启动子尚未被充分表征,迄今为止的研究表明,SREBP-1 在牛乳腺中的作用尚未区分 1a 和 1c 两种同工型。本研究旨在表征牛 SREBP-1c 启动子,并研究涉及肝 X 受体激动剂 T0901317 在 2 种不同牛乳腺上皮细胞系中调节 SREBP-1c 表达的 DNA 元件。含有野生型 SREBP-1c 启动子的荧光素酶报告基因构建体或含有突变的肝 X 受体反应元件或固醇反应元件的构建体被转染到 MacT 细胞和牛乳腺上皮(BME-UV)细胞中。我们已经证明,SREBP-1c 启动子中的肝 X 受体反应元件是介导 T0901317 反应所必需的,而固醇反应元件位点在该途径中仅发挥次要作用。本报告描述了牛 SREBP-1c 启动子及其在牛乳腺上皮细胞中受肝 X 受体的调节。

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