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Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes

Authors
 Jay D. Horton  ;  Nila A. Shah  ;  Joseph L. Goldstein  ;  Michael S. Brown  ;  Sahng Wook Park  ;  Norma N. Anderson  ;  Janet A. Warrington 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.100(21) : 12027-12032, 2003 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2003
MeSH
Animals ; CCAAT-Enhancer-Binding Proteins/genetics* ; Cholesterol/biosynthesis ; DNA-Binding Proteins/genetics* ; Fatty Acids/biosynthesis ; Gene Expression Profiling ; Intracellular Signaling Peptides and Proteins ; Liver/metabolism ; Male ; Membrane Proteins/deficiency* ; Membrane Proteins/genetics* ; Mice ; Mice, Knockout ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; Sterol Regulatory Element Binding Protein 1 ; Sterol Regulatory Element Binding Protein 2 ; Transcription Factors/genetics
Keywords
14512514
Abstract
The synthesis of fatty acids and cholesterol, the building blocks of membranes, is regulated by three membrane-bound transcription factors: sterol regulatory element-binding proteins (SREBP)-1a, -1c, and -2. Their function in liver has been characterized in transgenic mice that overexpress each SREBP isoform and in mice that lack all three nuclear SREBPs as a result of gene knockout of SREBP cleavage-activating protein (SCAP), a protein required for nuclear localization of SREBPs. Here, we use oligonucleotide arrays hybridized with RNA from livers of three lines of mice (transgenic for SREBP-1a, transgenic for SREBP-2, and knockout for SCAP) to identify genes that are likely to be direct targets of SREBPs in liver. A total of 1,003 genes showed statistically significant increased expression in livers of transgenic SREBP-1a mice, 505 increased in livers of transgenic SREBP-2 mice, and 343 showed decreased expression in Scap-/- livers. A subset of 33 genes met the stringent combinatorial criteria of induction in both SREBP transgenics and decreased expression in SCAP-deficient mice. Of these 33 genes, 13 were previously identified as direct targets of SREBP action. Of the remaining 20 genes, 13 encode enzymes or carrier proteins involved in cholesterol metabolism, 3 participate in fatty acid metabolism, and 4 have no known connection to lipid metabolism. Through application of stringent combinatorial criteria, the transgenic/knockout approach allows identification of genes whose activities are likely to be controlled directly by one family of transcription factors, in this case the SREBPs.
Files in This Item:
T200306780.pdf Download
DOI
10.1073/pnas.1534923100
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Sahng Wook(박상욱) ORCID logo https://orcid.org/0000-0002-9594-7074
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114459
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