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ChIP-seq in steatohepatitis and normal liver tissue identifies candidate disease mechanisms related to progression to cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2013 (English)In: BMC Medical Genomics, ISSN 1755-8794, E-ISSN 1755-8794, Vol. 6, 50- p.Article in journal (Refereed) Published
Abstract [en]

Background: Steatohepatitis occurs in alcoholic liver disease and may progress to liver cirrhosis and hepatocellular carcinoma. Its molecular pathogenesis is to a large degree unknown. Histone modifications play a key role in transcriptional regulations as marks for silencing and activation of gene expression and as marks for functional elements. Many transcription factors (TFs) are crucial for the control of the genes involved in metabolism, and abnormality in their function may lead to disease. Methods: We performed ChIP-seq of the histone modifications H3K4me1, H3K4me3 and H3K27ac and a candidate transcription factor (USF1) in liver tissue from patients with steatohepatitis and normal livers and correlated results to mRNA-expression and genotypes. Results: We found several regions that are differentially enriched for histone modifications between disease and normal tissue, and qRT-PCR results indicated that the expression of the tested genes strongly correlated with differential enrichment of histone modifications but is independent of USF1 enrichment. By gene ontology analysis of differentially modified genes we found many disease associated genes, some of which had previously been implicated in the etiology of steatohepatitis. Importantly, the genes associated to the strongest histone peaks in the patient were over-represented in cancer specific pathways suggesting that the tissue was on a path to develop to cancer, a common complication to the disease. We also found several novel SNPs and GWAS catalogue SNPs that are candidates to be functional and therefore needs further study. Conclusion: In summary we find that analysis of chromatin features in tissue samples provides insight into disease mechanisms.

Place, publisher, year, edition, pages
2013. Vol. 6, 50- p.
Keyword [en]
ChIP-seq, Tissue samples, Steatohepatitis, Cancer networks
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-215950DOI: 10.1186/1755-8794-6-50ISI: 000328896800003OAI: oai:DiVA.org:uu-215950DiVA: diva2:688806
Funder
Swedish Research Council, 521-2010-3505, 621-2011-6052Knut and Alice Wallenberg Foundation
Available from: 2014-01-17 Created: 2014-01-17 Last updated: 2017-12-06Bibliographically approved

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Bysani, Madhu Sudhan ReddyWallerman, OlaBornelöv, SusanneKomorowski, JanWadelius, Claes

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