eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways
- University of Manchester, United Kingdom
Abstract
Cancer is driven by both genetic and epigenetic changes that impact on gene expression profiles and the resulting tumourigenic phenotype. Enhancers are transcriptional regulatory elements that are key to our understanding of how this rewiring of gene expression is achieved in cancer cells. Here we have harnessed the power of RNA-seq data from hundreds of patients with oesophageal adenocarcinoma (OAC) or its precursor state Barrett's oesophagus (BO) coupled with open chromatin maps to identify potential enhancer RNAs (eRNAs) and their associated enhancer regions in this cancer. We identify ~1000 OAC-specific enhancers and use this data to uncover new cellular pathways that are operational in OAC. Among these are enhancers for JUP, MYBL2 and CCNE1, and we show that their activity is required for cancer cell viability. We also demonstrate the clinical utility of our dataset for identifying disease stage and patient prognosis. Our data therefore identify an important set of regulatory elements that enhance our molecular understanding of OAC and point to potential new therapeutic directions.
Data availability
All data have been deposited at ArrayExpress; OE19 KAS-seq and CUT&TAG data (E-MTAB-11357 and E-MTAB-11356, respectively) and OE19 HiC data (E-MTAB-12664).
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KAS-seq in OE19 cellsEBI ArrayExpress, E-MTAB-11357.
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CUT&TAG of OE19 cell lineEBI ArrayExpress, E-MTAB-11356.
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HiC data in OE19 cellsEBI ArrayExpress, E-MTAB-12664.
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Sequencing data for oesophageal and related samples - Ogden et al releaseEuropean Genome Phenome Archive, EGAD00001007496.
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ATAC-seq of oesophageal cell lines and tissue samplesEBI ArrayExpress, E-MTAB-5169.
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ATAC-seq of human Barrett's oesophagus tissueEBI ArrayExpress, E-MTAB-6751.
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ATAC-seq of oesophageal adenocarcinoma patient samplesEBI ArrayExpress, E-MTAB-8447.
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ChIP-seq of H3K27Ac in oesophageal adenocarcinoma OE19 cellsEBI ArrayExpress, E-MTAB-10319.
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ATAC-seq of oesophageal adenocarcinoma patient samplesEBI ArrayExpress, E-MTAB-8447.
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RNA-seq of OE19 cells treated with siNT or siKLF5 for 72 hoursEBI ArrayExpress, E-MTAB-8568.
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KLF5 ChIP-seq in CP-A and OE19 cellsEBI ArrayExpress, E-MTAB-8568.
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OE19 dnFOS RNA-seqEBI ArrayExpress, E-MTAB-10334.
Article and author information
Author details
Andrew D Sharrocks
Funding
Medical Research Council (MR/V010263/1)
- Samuel Ogden
Wellcome Trust (102171/B/13/Z)
- Ibrahim Ahmed
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Ahmed et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways
eLife 12:e80840.
https://doi.org/10.7554/eLife.80840
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