THE GENES COL4A5 AND COL4A6, CODING FOR BASEMENT-MEMBRANE COLLAGEN CHAINS ALPHA-5(IV) AND ALPHA-6(IV), ARE LOCATED HEAD-TO-HEAD IN CLOSE PROXIMITY ON HUMAN-CHROMOSOME XQ22 AND COL4A6 IS TRANSCRIBED FROM 2 ALTERNATIVE PROMOTERS
THE GENES COL4A5 AND COL4A6, CODING FOR BASEMENT-MEMBRANE COLLAGEN CHAINS ALPHA-5(IV) AND ALPHA-6(IV), ARE LOCATED HEAD-TO-HEAD IN CLOSE PROXIMITY ON HUMAN-CHROMOSOME XQ22 AND COL4A6 IS TRANSCRIBED FROM 2 ALTERNATIVE PROMOTERS
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DOI：
10.1073/pnas.91.24.11679
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发表时间：
1994-11-22
影响因子：
11.1
通讯作者：
NINOMIYA, Y
中科院分区：
文献类型：
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作者：
SUGIMOTO, M;OOHASHI, T;NINOMIYA, Y
人类基底膜 IV 型胶原蛋白的 α 5(IV) 和 α 6(IV) 链基因已在 X 染色体 q22 区段上一起发现，并据报道以头对头的方式排列。在这里，我们报告了 COL4A5 和 COL4A6 的 5' 侧翼序列，并且 COL4A6 以组织特异性方式从两个替代启动子转录。对转录起始位点上游序列的分析揭示了管家基因的一些特征，即缺乏 TATA 蛾以及 CCAAT 和 CTC 盒的存在。进一步分析表明，COL4A6 包含两个替代启动子，控制两个不同转录本的生成。一个转录起始位点（来自外显子 1'）距离 COL4A5 的转录起始位点 442 bp，而另一个转录起始位点（来自外显子 1）距离第一个转录起始位点 1050 bp，驱动第二个转录物的表达，该第二个转录物编码具有不同信号肽的 α 6(IV) 链。逆转录PCR实验表明，外显子1'的转录物在胎盘中丰富，而外显子1的转录物在肾脏和肺中更常见。这些结果为回答使用什么机制在不同组织中生成独特的基底膜结构的一般问题提供了额外的线索。
The genes for the alpha 5(IV) and alpha 6(IV) chains of human basement membrane collagen type IV have been found together on chromosome X at segment q22 and have been reported to be arranged in a head-to-head fashion. Here we report the 5' flanking sequences of COL4A5 and COL4A6 and that COL4A6 is transcribed from two alternative promoters in a tissue specific fashion. Analysis of the sequence immediately upstream of the transcription start sites revealed some features of housekeeping genes-i.e., the lack of a TATA moth and the presence of CCAAT and CTC boxes. Further analysis revealed that COL4A6 contains two alternative promoters that control the generation of two different transcripts. One transcription start site (from exon 1') is 442 bp away from the transcription start site of COL4A5, while an alternative transcription start site (from exon 1) is located 1050 bp from the first one and drives the expression of a second transcript that encodes an alpha 6(IV) chain with a different signal peptide. Reverse transcription-PCR experiments revealed that the transcript from exon 1' is abundant in placenta, whereas the transcript from exon 1 is more frequently found in kidney and lung. These results provide additional clues to answering the general question of what mechanisms are used to generate unique basement membrane structures in different tissues.