Brown K, Bailleul B, Ramsden M, Fee F, Krumlauf R, Balmain A
Beatson Institute for Cancer Research, Glasgow, Scotland.
Mol Carcinog. 1988;1(3):161-70. doi: 10.1002/mc.2940010304.
The complete 5' flanking region of the murine c-Ha-ras gene was cloned and sequenced. An untranslated exon (-1) was identified and the promoter region of the gene located. Like the rat and human homologues, the murine promoter is GC rich and contains several GC boxes together with a CAAT element, but lacks a TATA box, an arrangement similar to that found in many housekeeping genes. From primer extension studies, the gene was shown to have three transcriptional start sites, whose positions differ from those previously found for the human gene. No alterations in these start sites were detected between the normal gene and activated Ha-ras genes from mouse skin tumors. A region of strong homology between mouse, rat, and human Ha-ras genes exists within the large intron separating exon (-1) from the first coding exon. In addition, from chloramphenicol acetyltransferase assays, the upstream region has promoter activity which appears to be enhanced by the inclusion of sequences within this intron.
克隆并测序了小鼠c-Ha-ras基因完整的5'侧翼区域。鉴定出一个非翻译外显子(-1)并确定了该基因的启动子区域。与大鼠和人类同源物一样,小鼠启动子富含GC,包含几个GC盒以及一个CAAT元件,但缺少TATA盒,这种排列类似于许多管家基因中的情况。通过引物延伸研究表明,该基因有三个转录起始位点,其位置与先前在人类基因中发现的不同。在正常基因与来自小鼠皮肤肿瘤的活化Ha-ras基因之间未检测到这些起始位点的改变。在将外显子(-1)与第一个编码外显子分开的大内含子内,小鼠、大鼠和人类Ha-ras基因之间存在高度同源区域。此外,通过氯霉素乙酰转移酶测定,上游区域具有启动子活性,而包含该内含子内的序列似乎可增强这种活性。