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Papers In Press, published online ahead of print August 1, 2003
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Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10021
Corresponding Author: maxwelk{at}rockefeller.edu
High cholesterol diets elicit changes in gene expression via such transcription factors as SREBPs and LXRs. We used Affymetrix microarrays to identify genes in mouse liver regulated by dietary cholesterol (0.0% versus 0.5% cholesterol wt/wt). Three independent experiments were performed and data were analyzed with Affymetrix Microarray Suite and ANOVA statistical software. There were 69 unique Unigene clusters consistently regulated by dietary cholesterol (37 down-regulated and 32 up-regulated). The array results were confirmed by quantitative RT-PCR (Q-PCR) for seven of nine down-regulated genes and five of six up-regulated genes. A time course of dietary cholesterol feeding over one week revealed different temporal patterns of gene regulation for these confirmed genes. Six down-regulated genes were examined in transgenic mice over-expressing truncated nuclear forms of SREBP-1a and SREBP-2, and all were induced in these mice. A second microarray analysis of mice treated with the LXR agonist TO901317 confirmed that 13 of the 32 cholesterol up-regulated genes were also LXR activated. This array result was confirmed by Q-PCR for three of three genes. In summary, these studies identified and confirmed six novel dietary cholesterol-regulated genes, three putative SREBP target genes (Camk1d, Fabp5, and Pcsk9) and three putative LXR target genes (Adam11, Api6, and Fbxo3).
Revised on July 25, 2003
Accepted on July 25, 2003
Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice
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