The caudal-type homeobox protein Cdx-2 binds to the colon promoter of the carbonic anhydrase 1 gene
The caudal-type homeobox protein Cdx-2 binds to the colon promoter of the carbonic anhydrase 1 gene
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DOI：
10.1111/j.1432-1033.1996.t01-1-00670.x
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发表时间：
1996-03-01
期刊：
影响因子：
--
通讯作者：
Edwards, YH
中科院分区：
文献类型：
--
作者：
Drummond, F;Sowden, J;Edwards, YH
碳酸酐酶1（Carbonic anhydrase 1，CA 1）是结肠上皮细胞中含量丰富的一种酶。在胃肠道中，碳酸酐酶对于NaCl的再吸收、肠道内容物的碱化和短链脂肪酸的吸收至关重要。CAI基因具有两个启动子，其中一个在结肠上皮中特异性地有活性，另一个在红系细胞中特异性地有活性。我们正在研究从结肠特异性启动子调节CA 1表达的因素。结肠特异性脱氧核糖核酸酶I超敏位点（DHS）已被映射到接近结肠转录起始位点（DHS 6c）和上游内含子（HS 5c）。使用电泳迁移率变动分析，以搜索650 bp的区域，其中包含DHS 6C，我们已经确定了序列，结合结肠特异性因子（COF 1），并通过缺失分析，我们已经缩小了COF 1结合基序到一个17 bp的序列。这个基序与蔗糖酶-异麦芽糖酶基因启动子中的蛋白结合基序的比较、竞争测定和抗体研究表明COF 1与同源结构域蛋白Cdx-2相同。我们认为Cdx-2在CA 1的丝氨酸特异性表达中起着重要作用。
Carbonic anhydrase 1 (CA1) is an abundant enzyme in colon epithelia. In the gastrointestinal tract, carbonic anhydrase is vital for NaCl resorption, alkalinization of gut contents, and absorption of short-chain fatty acids. The CAI gene has two promoters, one of which is specifically active in colon epithelia and the other in erythroid cells. We are investigating the factors that regulate CA1 expression from the colon-specific promoter. Colon-specific deoxyribonuclease I hypersensitive sites (DHS) have been mapped close to the colon transcription initiation site (DHS6c) and in the upstream intron (HS5c). Using electrophoretic mobility-shift assays to search the 650-bp region which contains DHS6c, we have identified sequences that bind a colon-specific factor (COF1) and by deletion analysis we have narrowed down the COF1-binding motif to a 17-bp sequence. A comparison of this motif with a protein-binding motif in the sucrase-isomaltase gene promoter, competition assays, and antibody studies indicate that COF1 is identical to the homeodomain protein Cdx-2. We propose that Cdx-2 plays an important role in the intestine-specific expression of CA1.