Comparison of intestinal phospholipase A/lysophospholipase and sucrase-isomaltase genes suggest a common structure for enterocyte-specific promoters.
Comparison of intestinal phospholipase A/lysophospholipase and sucrase-isomaltase genes suggest a common structure for enterocyte-specific promoters.
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肠磷脂酶 A/溶血磷脂酶和蔗糖酶-异麦芽糖酶基因的比较表明肠细胞特异性启动子具有共同的结构。
DOI：
10.1089/dna.1997.16.1419
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发表时间：
1997
影响因子：
3.1
通讯作者：
Traber,PG
中科院分区：
文献类型：
--
作者：
Taylor,JK;Boll,W;Levy,T;Suh,E;Siang,S;Mantei,N;Traber,PG
肠磷脂酶A/溶血磷脂酶（IPAL）是一种发育过程中表达的精氨酸特异性刷状缘酶，其表达模式与另一种特征性的刷状缘酶蔗糖酶-异麦芽糖酶（SI）相似，并沿着肠隐窝-绒毛轴表达。一个组织特异性的DNase I超敏位点被确定在染色质从肠核直接上游的IPAL基因的转录起始位点。足迹分析表明，在IPAL启动子内的两个DNA元件被肠核蛋白保护。IPAL-FP 1元件被证明是Cdx 1和Cdx 2，甜菜碱特异性同源盒蛋白的单体结合位点。此外，该位点对于通过与Cdx蛋白相互作用在肠细胞系中转录激活启动子是重要的。来自肝脏和肠的核蛋白与IPAL-FP 2元件相互作用，形成与HNF 1结合一致的复合物。Cdx和HNF 1结合位点也被证明是负责SI基因启动子转录激活的两个主要调控元件，SI基因启动子在转基因小鼠中指导精氨酸特异性转录。这些研究结果表明，肠上皮细胞的基因表达在类似的发展模式可能是由共同的DNA元件和它们相关的转录因子的相互作用进行调节。
Intestinal phospholipase A/lysophospholipase (IPAL) is an intestine-specific brush-border enzyme expressed during development and along the intestinal crypt-villus axis in a pattern similar to another well characterized brush-border enzyme, sucrase-isomaltase (SI). A tissue-specific DNase I hypersensitive site was identified in chromatin from intestinal nuclei immediately upstream from the transcriptional start site of the IPAL gene. Footprinting analysis showed that two DNA elements within the IPAL promoter were protected by intestinal nuclear proteins. The IPAL-FP1 element was shown to be a monomer binding site for Cdx1 and Cdx2, intestine-specific homeobox proteins. Moreover, this site was important for transcriptional activation of the promoter in intestinal cell lines via interaction with Cdx proteins. Nuclear proteins from both liver and intestine interacted with the IPAL-FP2 element, forming a complex consistent with binding to HNF1. Cdx and HNF1 binding sites have also been shown to be the two major regulatory elements responsible for transcriptional activation of the SI gene promoter, which directs intestine-specific transcription in transgenic mice. These findings suggest that enterocyte genes that are expressed in similar developmental patterns may be regulated by the interaction of common DNA elements and their associated transcription factors.