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Identification of Novel Genes and Pathways Regulating SREBP Transcriptional Activity.

Chatterjee, S; Szustakowski, JD; Nanguneri, NR; Mickanin, C; Labow, MA; Nohturfft, A; Dev, KK; Sivasankaran, R (2009) Identification of Novel Genes and Pathways Regulating SREBP Transcriptional Activity. PLOS ONE, 4 (4). e5197. ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0005197
SGUL Authors: Nohturfft, Axel

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Abstract

BACKGROUND: Lipid metabolism in mammals is orchestrated by a family of transcription factors called sterol regulatory element-binding proteins (SREBPs) that control the expression of genes required for the uptake and synthesis of cholesterol, fatty acids, and triglycerides. SREBPs are thus essential for insulin-induced lipogenesis and for cellular membrane homeostasis and biogenesis. Although multiple players have been identified that control the expression and activation of SREBPs, gaps remain in our understanding of how SREBPs are coordinated with other physiological pathways. METHODOLOGY: To identify novel regulators of SREBPs, we performed a genome-wide cDNA over-expression screen to identify proteins that might modulate the transcription of a luciferase gene driven from an SREBP-specific promoter. The results were verified through secondary biological assays and expression data were analyzed by a novel application of the Gene Set Enrichment Analysis (GSEA) method. CONCLUSIONS/SIGNIFICANCE: We screened 10,000 different cDNAs and identified a number of genes and pathways that have previously not been implicated in SREBP control and cellular cholesterol homeostasis. These findings further our understanding of lipid biology and should lead to new insights into lipid associated disorders.

Item Type: Article
Additional Information: ©2009 Chatterjee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Base Sequence, Cell Line, Cholesterol, DNA, Complementary, Homeostasis, Humans, Promoter Regions, Genetic, Signal Transduction, Sterol Regulatory Element Binding Proteins, Transcription, Genetic, Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: PLOS ONE
ISSN: 1932-6203
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Dates:
DateEvent
21 April 2009Published
Web of Science ID: WOS:000265513800001
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URI: http://openaccess.sgul.ac.uk/id/eprint/947
Publisher's version: https://doi.org/10.1371/journal.pone.0005197

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