Two genes, COL4A3 and COL4A4 coding for the human α3(IV) and α4(IV) collagen chains are arranged head-to-head on chromosome 2q36
Two genes, COL4A3 and COL4A4 coding for the human α3(IV) and α4(IV) collagen chains are arranged head-to-head on chromosome 2q36
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DOI：
10.1016/s0014-5793(98)00128-8
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发表时间：
1998-03-06
期刊：
影响因子：
3.5
通讯作者：
Ninomiya, Y
中科院分区：
文献类型：
--
作者：
Momota, R;Sugimoto, M;Ninomiya, Y
我们首先分离并鉴定了分别编码人基底膜α 3（IV）和α 4（IV）胶原链的COL4A3和COL4A4 5'侧序列的基因组DNA片段。核苷酸序列分析表明，这两个基因是头对头排列的。为了确定COL4A4基因的转录起始位点，我们进行了RACE和RNase保护实验，表明有两个备选转录本可能来自两个不同的启动子。有趣的是，COL4A4的一个转录起始位点（来自外显子1’）距离COL4A3报道的转录起始位点仅5bp，而另一个转录物（来自外显子1）从第一个转录物下游373个核苷酸开始，产生了在5’UTR区域不同的两种转录物。这两种转录物的表达是组织特异性的；外显子1转录本主要在上皮细胞中表达，而外显子1’转录本普遍存在且低表达。启动子区域的核苷酸序列由密集的CpG二核苷酸、GC盒、CTC盒和CCAAT盒组成，但没有TATA盒。这些结果为描述六种IV型胶原基因的组织特异性表达和基底膜组装的启动子活性提供了信息。(C) 1998年欧洲生化学会联合会。
We first isolated and characterized genomic DNA fragments that cover the 5' flanking sequences of COL4A3 and COL4A4 encoding the human basement membrane alpha 3(IV) and alpha 4(IV) collagen chains, respectively. Nucleotide sequence analysis indicated that the two genes are arranged head-to-head. To determine transcription start site for COL4A4 gene, we performed RACE and RNase protection assays, indicating that there are two alternative transcripts presumably derived from two different promoters. Interestingly, one transcription start site (from exon 1') of COL4A4 is only 5 bp away from the reported transcription start site of COL4A3, whereas the other transcript (from exon 1) starts 373 nucleotides downstream from the first one, generating the two kinds of transcripts that differ in the 5' UTR regions. Expression of these two transcripts appears tissue-specific; exon 1 transcript was expressed predominantly in epithelial cells, while exon 1' transcript showed rather ubiquitous and low expression. The nucleotide sequence of the promoter region is composed of dense CpG dinucleotides, GC boxes, CTC boxes and a CCAAT box but no TATA box. These results provide information to delineate the promoter activity for the tissue-specific expression of the six type IV collagen genes and basement membrane assembly in different tissues and organs. (C) 1998 Federation of European Biochemical Societies.