Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Bysani M

PROVIDER: S-EPMC3831757 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Bysani Madhusudhan M Wallerman Ola O Bornelöv Susanne S Zatloukal Kurt K Komorowski Jan J Wadelius Claes C

BMC medical genomics 20131108

<h4>Background</h4>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 ...[more]

PMID: 24206787

Similar Datasets

Project description:Cardiac fibrosis is a common pathological feature in cardiac remodeling. This study aimed to explore the role of KDM5A in cardiac fibrosis via bioinformatics analysis. Cardiac fibroblasts (CFs) were harvested and cultured from 10 dilated cardiomyopathy (DCM) patients who underwent heart transplantation. Western blotting was applied to verify that KDM5A is regulated by angiotensin II (Ang II) via the PI3k/AKT signaling pathway. The differentially expressed genes (DEGs) were analyzed by transcriptomics. ChIP-seq and ChIP-qPCR were used to identify the genes bound by KDM5A. In integrative analysis, weighted gene coexpression network analysis (WGCNA) was performed to identify highly relevant gene modules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the key genes in modules. The STRING database, Cytoscape, and MCODE were applied to construct the protein-protein interaction (PPI) network and screen hub genes. To verify the expression of DEGs regulated by KDM5A, Western blotting and immunofluorescence were performed in myocardial tissue samples. Immunofluorescence verified the vimentin positivity of CFs. Ang II upregulated the expression of KDM5A in CFs via the PI3K/AKT signaling pathway. GO analysis of DEGs indicated that regulation of vasoconstriction, extracellular region, and calcium ion binding were enriched when KDM5A interfered with CPI or Ang II. KEGG analysis of the DEGs revealed the involvement of ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, cell adhesion, and arrhythmogenic right ventricular cardiomyopathy pathways. Three hub genes (IGF1, MYH11, and TGFB3) were identified via four different algorithms. Subsequent verification in patient samples demonstrated that the hub genes, which were regulated by KDM5A, were downregulated in DCM samples. KDM5A is a key regulator in the progression of cardiac fibrosis. In this successful integrative analysis, IGF1, MYH11, and TGFB3 were determined to be coordinately expressed to participate in cardiac fibrosis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets