cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine
cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine
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DOI：
10.1074/jbc.m204935200
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发表时间：
2002-09-06
影响因子：
4.8
通讯作者：
Gumucio, DL
中科院分区：
文献类型：
--
作者：
Madison, BB;Dunbar, L;Gumucio, DL
绒毛蛋白是一种在吸收组织的顶端刷状缘中发现的肌动蛋白捆绑蛋白，是在胚胎肠内胚层中最早被转录激活的结构基因之一。在成年个体中，绒毛蛋白在肠道上皮的每个细胞中广泛表达，无论是在肠道的纵轴（隐窝到绒毛顶端）还是横轴（十二指肠到结肠）。在此，我们证明小鼠绒毛蛋白基因的一个12.4千碱基区域可驱动两种不同的报告基因（LacZ和Cre重组酶）在转基因小鼠的整个肠道上皮中高水平表达。该转基因的一部分缺失会导致小肠（十二指肠）和大肠（盲肠）特定区域的β -半乳糖苷酶活性降低。此外，整个肠道隐窝部分的表达也降低。因此，绒毛蛋白在肠道中的整体表达模式显然是不同的和特定区域的控制过程融合的结果。也就是说，绒毛蛋白在十二指肠和盲肠中的表达与肠道其他部分需要不同的调控序列，并且绒毛蛋白在隐窝中的表达与在绒毛顶端的表达由不同的调控回路所调控。
Villin, an actin bundling protein found in the apical brush border of absorptive tissues, is one of the first structural genes to be transcriptionally activated in the embryonic intestinal endoderm. In the adult, villin is broadly expressed in every cell of the intestinal epithelium on both the vertical axis (crypt to villus tip) and the horizontal axis (duodenum through colon) of the intestine. Here, we document that a 12.4-kilobase region of the mouse villin gene drives high level expression of two different reporter genes (LacZ and Cre recombinase) within the entire intestinal epithelium of transgenic mice. Deletion of a portion of this transgene results in reduction of beta-galactosidase activity in restricted domains of the small intestine (duodenum) and large intestine (cecum). In addition, expression is reduced in the crypt compartment throughout the intestine. Thus, the global expression pattern of villin in the intestine is apparently the consequence of an amalgam of distinct and individual domain-specific control processes. That is, expression of villin in the duodenum and cecum requires different regulatory sequences than the rest of the intestine, and the expression of villin in crypts is regulated by different circuitry than expression of villin on villus tips.