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Novel genes in cell cycle control and lipid metabolism with dynamically regulated binding sites for sterol regulatory element-binding protein 1 and RNA polymerase II in HepG2 cells detected by chromatin immunoprecipitation with microarray detection
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. (Wadelius)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics. (Komorowski)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Ericsson)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics. (Komorowski)
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2009 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 7, 1878-1890 p.Article in journal (Refereed) Published
Abstract [en]

Sterol regulatory element-binding proteins 1 and 2 (SREBP-1 and SREBP-2) are important regulators of genes involved in cholesterol and fatty acid metabolism, but have also been implicated in the regulation of the cell cycle and have been associated with the pathogenesis of type 2 diabetes, atherosclerosis and obesity, among others. In this study, we aimed to characterize the binding sites of SREBP-1 and RNA polymerase II through chromatin immunoprecipitation and microarray analysis in 1% of the human genome, as defined by the Encyclopaedia of DNA Elements consortium, in a hepatocellular carcinoma cell line (HepG2). Our data identified novel binding sites for SREBP-1 in genes directly or indirectly involved in cholesterol metabolism, e.g. apolipoprotein C-III (APOC3). The most interesting biological findings were the binding sites for SREBP-1 in genes for host cell factor C1 (HCFC1), involved in cell cycle regulation, and for filamin A (FLNA). For RNA polymerase II, we found binding sites at classical promoters, but also in intergenic and intragenic regions. Furthermore, we found evidence of sterol-regulated binding of SREBP-1 and RNA polymerase II to HCFC1 and FLNA. From the results of this work, we infer that SREBP-1 may be involved in processes other than lipid metabolism.

Place, publisher, year, edition, pages
2009. Vol. 276, no 7, 1878-1890 p.
Keyword [en]
HCFC1, human, intragenic binding, sterolregulated, transcriptional regulation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-99754DOI: 10.1111/j.1742-4658.2009.06914.xISI: 000264021900008PubMedID: 19292868OAI: oai:DiVA.org:uu-99754DiVA: diva2:208741
Available from: 2009-03-19 Created: 2009-03-19 Last updated: 2017-12-13Bibliographically approved

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Enroth, StefanPunga, TanelWadelius, Claes

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Department of Genetics and PathologyThe Linnaeus Centre for BioinformaticsLudwig Institute for Cancer ResearchDepartment of Medical Biochemistry and Microbiology
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