ChIP-seq in steatohepatitis and normal liver tissue identifies candidate disease mechanisms related to progression to cancer

BMC Medical Genomics

Claes Wadelius²  Jan Komorowski³  Kurt Zatloukal¹  Susanne Bornelöv⁴  Ola Wallerman⁵  Madhusudhan Bysani² 

[1] Institute of Pathology, Medical University of Graz, Graz, Austria;Science for Life Laboratory, Department of Immunology, Genetics and Pathology, BMC, Uppsala University, PO BOX 815, Uppsala, SE 751 08, Sweden;Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Warsaw, PL-02-106, Poland;Science for Life Laboratory, Department of Cell and Molecular Biology, BMC, Uppsala University, Uppsala, Sweden;Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, BMC, Uppsala, Sweden

关键词: Cancer networks;    Steatohepatitis;    Tissue samples;    ChIP-seq;   

Others  :  1091343
DOI  :  10.1186/1755-8794-6-50

 received in 2013-06-25, accepted in 2013-10-31,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Bysani et al.; licensee BioMed Central Ltd.

【 图 表 】

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