ChIP-seq In Steatohepatitis And Normal Liver Tissue Identifies Candidate Disease Mechanisms Related To Progression To Cancer

Madhusudhan Bysani, Ola Wallerman, Susanne Bornelöv, Kurt Zatloukal, Jan Komorowski, and Claes Wadelius.
BMC Medical Genomics. 2013-11-08;6(50)
Abstract
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. 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.
Consortium data used in this publication
SRA066400