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Comparative genome analysis of potential regulatory elements in the ABCG5-ABCG8 gene cluster
Alan T Remaley1, Samantha Bark, Avram D Walts
1National Heart, Lung and Blood Institute, National Institutes of Health, Bldg. 10/2C-433, 10 Center Drive, Bethesda, MD 20892, USA. aremaley@nih.gov
Abstract:
The excretion of sterols from the liver and intestine is regulated by the ABCG5 and ABCG8 transporters. To identify potential regulatory elements, 152 kb 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 as 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.