KMID : 0624620130460060322
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BMB Reports 2013 Volume.46 No. 6 p.322 ~ p.327
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Cooperative transcriptional activation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 genes by nuclear receptors including Liver-X-Receptor
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Back Su-Sun
Kim Jin-Su Choi Dae-Hyung Lee Eui-Sup Choi Soo-Young Han Kyu-Hyung
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Abstract
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The ATP-binding cassette transporters ABCG5 and ABCG8 form heterodimers that limit absorption of dietary sterols in the intestine and promote cholesterol elimination from the body through hepatobiliary secretion. To identify cis-regulatory elements of the two genes, we have cloned and analyzed twenty-three evolutionary conserved region (ECR) fragments using the CMV-luciferase reporter system in HepG2 cells. Two ECRs were found to be responsive to the Liver-X-Receptor (LXR). Through elaborate deletion studies, regions containing putative LXREs were identified and the binding of LXR¥á was demonstrated by EMSA and ChIP assay. When the LXREs were inserted upstream of the intergenic promoter, synergistic activation by LXR¥á/RXR¥á in combination with GATA4, HNF4¥á, and LRH-1, which had been shown to bind to the intergenic region, was observed. In conclusion, we have identified two LXREs in ABCG5/ABCG8 genes for the first time and propose that these LXREs, especially in the ECR20, play major roles in regulating these genes.
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KEYWORD
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ABCG5, ABCG8, Cholesterol, LXR, Transcription
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