Structural characterisation of the mouse nuclear oxysterol receptor genes LXRα and LXRβ
Structural characterisation of the mouse nuclear oxysterol receptor genes LXRα and LXRβ
复制标题
DOI：
10.1016/s0378-1119(99)00555-7
复制
发表时间：
2000-02-08
期刊：
影响因子：
3.5
通讯作者：
Gustafsson, JÅ
中科院分区：
文献类型：
--
作者：
Alberti, S;Steffensen, KR;Gustafsson, JÅ
氧甾醇是胆固醇稳态、胆汁酸合成和细胞凋亡等多种生物过程的重要调节分子。最近的研究结果表明，其中一些功能是由核受体 LXR α 和 LXR β 介导的，因为它们有可能结合一组天然存在的氧甾醇作为其配体。在本报告中，我们比较了两个小鼠 LXR 基因的基因组结构和启动子区域。此外，我们还发现了小鼠基因组中存在加工但截短的 LXR beta 假基因的证据。小鼠肝脏 cDNA 上的 RACE-PCR 表明两种基因都存在多个确定的转录起始位点。 LXR α 和 LXR β 启动子区域富含 GC，并包含许多推定的 Sp1 结合位点，但缺乏明显的 TATA 和 CAAT 盒。数据库搜索揭示了 LXR 启动子区域中的几个序列基序，这些基序类似于已知的转录因子结合位点。最引人注目的是在 LXR beta 启动子中鉴定出一个潜在的 NF kappa B 和七个潜在的 Ets 蛋白结合位点，表明该受体在造血/免疫系统中发挥着重要作用。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Oxysterols are important regulatory molecules of diverse biological processes such as cholesterol homeostasis, bile acid synthesis and apoptosis. Recent findings led to the suggestion that some of these functions are mediated by the nuclear receptors LXR alpha and LXR beta owing to their potential to bind a group of naturally occurring oxysterols as their ligands. In this report, we compare the genomic structure and the promoter regions of the two mouse LXR genes. In addition, we show evidence for the presence of a processed, but truncated LXR beta pseudogene in the mouse genome. RACE-PCR on mouse liver cDNA demonstrates the presence of more than one defined transcription initiation site for both genes. The LXR alpha and LXR beta promoter regions are GC-rich and contain a number of putative Sp1 binding sites but lack obvious TATA and CAAT boxes. A database search revealed several sequence motifs in the LXR promoter regions that resemble known transcription factor binding sites. Most striking is the identification of one potential NF kappa B and seven potential Ets-protein binding sites in the LXR beta promoter, suggesting an important role for this receptor in the haematopoietic/immune system. (C) 2000 Elsevier Science B.V. All rights reserved.