Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors

The spreading of epigenetic domains has emerged as a distinguishing epigenomic phenotype for diverse cell types. In particular, clusters of H3K27ac- and H3K4me3-marked elements, referred to as super-enhancers, and broad H3K4me3 domains, respectively, have been linked to cell identity and disease sta...

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Published inEpigenomes Vol. 3; no. 2; p. 11
Main Authors Gerrard, Diana L, Boyd, Joseph R, Stein, Gary S, Jin, Victor X, Frietze, Seth
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.06.2019
MDPI
Subjects
Acetylation
Adenocarcinoma
Cell culture
Cell cycle
Enhancers
Epigenetics
epigenomics
Gene expression
Genomes
Genomic analysis
Growth factors
Histone acetyltransferase
Pancreatic cancer
Patients
Phenotypes
super-enhancers
Survival analysis
Tumor cell lines
epigenomics
pancreatic cancer
super-enhancers
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Summary:The spreading of epigenetic domains has emerged as a distinguishing epigenomic phenotype for diverse cell types. In particular, clusters of H3K27ac- and H3K4me3-marked elements, referred to as super-enhancers, and broad H3K4me3 domains, respectively, have been linked to cell identity and disease states. Here, we characterized the broad domains from different pancreatic ductal adenocarcinoma (PDAC) cell lines that represent distinct histological grades. Our integrative genomic analysis found that human derived cell line models for distinct PDAC grades exhibit characteristic broad epigenetic features associated with gene expression patterns that are predictive of patient prognosis and provide insight into pancreatic cancer cell identity. In particular, we find that genes marked by overlapping Low-Grade broad domains correspond to an epithelial phenotype and hold potential as markers for patient stratification. We further utilize ChIP-seq to compare the effects of histone acetyltransferase (HAT) inhibitors to detect global changes in histone acetylation and methylation levels. We found that HAT inhibitors impact certain broad domains of pancreatic cancer cells. Overall, our results reveal potential roles for broad domains in cells from distinct PDAC grades and demonstrate the plasticity of particular broad epigenomic domains to epigenetic inhibitors.
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ISSN:2075-4655
2075-4655
DOI:10.3390/epigenomes3020011