Funk C D, Hoshiko S, Matsumoto T, Rdmark O, Samuelsson B
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1989 Apr;86(8):2587-91. doi: 10.1073/pnas.86.8.2587.
The gene for human 5-lipoxygenase has been isolated from three different bacteriophage genomic libraries and a genomic cosmid library. The gene spans greater than 82 kilobases and consists of 14 exons. The size range for the exons is 82-613 base pairs, whereas that for the introns is approximately 200 bp to greater than 26 kb. A major site of transcription initiation in leukocytes was mapped to a thymidine residue 65 base pairs upstream of the ATG initiation codon by nuclease S1 protection and primer extension experiments. Other potential minor initiation sites were found. The putative promoter region contains no TATA and CCAAT sequences in the expected positions upstream of the major transcription initiation site but contains multiple GC boxes within a (G + C)-rich region, as does the immediate 5' region of the first intron. Characteristics common to the 5' end of the human 5-lipoxygenase gene and the promoter regions of the housekeeping genes raise important questions concerning the regulation of 5-lipoxygenase gene expression.
人类5-脂氧合酶基因已从三个不同的噬菌体基因组文库和一个基因组黏粒文库中分离出来。该基因跨度超过82千碱基对,由14个外显子组成。外显子的大小范围为82 - 613个碱基对,而内含子的大小范围约为200 bp至大于26 kb。通过核酸酶S1保护和引物延伸实验,将白细胞中转录起始的主要位点定位到ATG起始密码子上游65个碱基对处的一个胸苷残基。还发现了其他潜在的次要起始位点。推测的启动子区域在主要转录起始位点上游的预期位置没有TATA和CCAAT序列,但在富含(G + C)的区域内含有多个GC框,第一个内含子的紧邻5'区域也是如此。人类5-脂氧合酶基因5'端与管家基因启动子区域共有的特征,引发了有关5-脂氧合酶基因表达调控的重要问题。