Byrd P J, Cooper P R, Stankovic T, Kullar H S, Watts G D, Robinson P J, Taylor M R
CRC Institute for Cancer Studies, University of Birmingham Medical School, UK.
Hum Mol Genet. 1996 Nov;5(11):1785-91. doi: 10.1093/hmg/5.11.1785.
In an earlier report we showed that the 5' end of the gene for ataxia telangiectasia ATM is within 700 bp of the 5' end of a novel gene E14, and suggested that the CpG island that separates these genes functions as a bidirectional promoter. We have now determined the complete amino acid sequence of the E14 protein, defined the exon/intron structure of the gene and estimate that the complete gene is more than 55 kb in length. The E14 gene appears to be a housekeeping gene that is expressed in all tissues, including all parts of the brain. The E14/ATM promoter organisation is conserved in man, monkey and mouse, although the mouse promoter is more compact and appears to lack two of the four putative Sp1 boxes found in the human promoter. Reporter gene constructs showed that the human and mouse E14/ATM promoters were indeed bidirectional, that the ATM side of the human promoter was three times stronger than the E14 side, and that the mouse promoter (in human cells) directed transcription with equal efficiency in both directions, but at a lower level than the human promoter. Analysis of a small number of A-T patients for mutations in the promoter region or the E14 coding sequence did not provide evidence to suggest that E14 contributes to the A-T phenotype.
在一份较早的报告中，我们表明共济失调毛细血管扩张症基因ATM的5'端位于一个新基因E14的5'端的700 bp范围内，并提出分隔这些基因的CpG岛起着双向启动子的作用。我们现已确定了E14蛋白的完整氨基酸序列，明确了该基因的外显子/内含子结构，并估计完整基因长度超过55 kb。E14基因似乎是一个管家基因，在包括脑的所有部分在内的所有组织中均有表达。尽管小鼠启动子更为紧凑，且似乎缺少人类启动子中四个假定的Sp1框中的两个，但E14/ATM启动子结构在人、猴和小鼠中是保守的。报告基因构建体显示，人类和小鼠的E14/ATM启动子确实是双向的，人类启动子的ATM一侧比E14一侧强三倍，并且小鼠启动子（在人类细胞中）在两个方向上指导转录的效率相同，但水平低于人类启动子。对少数共济失调毛细血管扩张症患者的启动子区域或E14编码序列中的突变进行分析，未提供证据表明E14与共济失调毛细血管扩张症的表型有关。
