Comparative genome analysis of potential regulatory elements in the ABCG5-ABCG8 gene cluster

被引:46
作者
Remaley, AT
Bark, S
Walts, AD
Freeman, L
Shulenin, S
Annilo, T
Elgin, E
Rhodes, HE
Joyce, C
Dean, M
Santamarina-Fojo, S
Brewer, HB
机构
[1] NHLBI, NIH, Bethesda, MD 20892 USA
[2] NCI, Lab Genom Divers, NIH, Frederick, MD USA
[3] Walter Reed Army Med Ctr, Walter Reed Army Med Ctr, Dept Med, Serv Cardiol, Washington, DC USA
关键词
sitosterolemia; phytosterols; ABCG5; ABCG8; ABC transporter;
D O I
10.1016/S0006-291X(02)00652-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
The excretion of sterols from the liver and intestine is regulated by the ABCG5 and ABCG8 transporters. To identify potential regulatory elements, 152kb of the human ABCG5-ABCG8 gene cluster was sequenced and comparative genome analysis was performed. The two genes are oriented in a head-to-head configuration and are separated by a 374-bp intergenic region, which is highly conserved among several species. Using a reporter construct, the intergenic region was found to act as a bidirectional promoter. A conserved GATA site in the intergenic region was shown by site-directed mutagenesis to act Lis a repressor for the ABCG5 promoter. The intergenic region was also shown to be partially responsive to treatment by LXR agonists. In Summary, several potential regulatory elements were found for the ABCG5 and ABCG8 genes. and the intergenic region was found to act as a bidirectional promoter. Published by Elsevier Science (USA).
引用
收藏
页码:276 / 282
页数:7
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