TRANSCRIPTOME 2002: From Functional Genomics to Systems
Identification of Genes in Biosynthesis of Fatty Acids and Cholesterol Pathways Using Microarrays
Nila A. Shah1, Young-Ah Moon2, Suchismita Mohapatra2, Jay D. Horton2, and Janet A. Warrington1, 1Health Management Research, Affymetrix Inc., Santa Clara, CA, 2Dept of Molecular Genetics, Internal Medicine and Biochemistry, University of Texas South Western Medical Center, Dallas, TX
Sterol regulatory binding proteins (SREBP) are a family of basic helix-loop-helix leucine zipper transcription factors that regulate biosynthesis of fatty acids and cholesterol. To identify candidate genes in the fatty acid synthesis pathway, transgenic mice over expressing SREBP-1a and SREBP-2 isofroms in liver were used. Labeled cRNA was prepared from liver and hybridized to mouse expression microarrays interrogating ~30,000 genes/ESTs. Some of the known genes, ACC, FAS, and ATP citrate lyase regulated by over expression of SREBP were identified by microarray analysis. A novel gene, long chain fatty acyl elongase (LCE) regulated by the SREBP1a and 2 was also identified. LCE was over expressed with a fold change of 25 and 9 in SREBP-1a and SREBP-2 mice respectively. The confirmation of LCE was done by northern blot analysis, sequence homology searches and biochemical tests. This enzyme specifically catalyzes the elongation of 12, 14 and 16 carbons but does not elongate the C-18 fatty acids or very long chain fatty acids.
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