Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma

PLoS Genet. 2017 Aug 31;13(8):e1006879. doi: 10.1371/journal.pgen.1006879. eCollection 2017 Aug.

Abstract

Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, genes encoding chromatin remodeling enzymes are frequently mutated in OAC. This is consistent with the emerging concept that cancer cells exhibit reprogramming of their chromatin environment which leads to subsequent changes in their transcriptional profile. Here, we have used ATAC-seq to interrogate the chromatin changes that occur in OAC using both cell lines and patient-derived material. We demonstrate that there are substantial changes in the regulatory chromatin environment in the cancer cells and using this data we have uncovered an important role for ETS and AP1 transcription factors in driving the changes in gene expression found in OAC cells.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenovirus E1A Proteins / genetics*
  • Cell Line, Tumor
  • Chromatin / genetics
  • Chromatin Assembly and Disassembly / genetics
  • DNA-Binding Proteins / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • Humans
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ets
  • Transcription Factor AP-1 / genetics*
  • Transcription Factors / genetics*
  • Transcriptional Activation / genetics

Substances

  • Adenovirus E1A Proteins
  • Chromatin
  • DNA-Binding Proteins
  • ETV1 protein, human
  • ETV4 protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Transcription Factor AP-1
  • Transcription Factors

Supplementary concepts

  • Adenocarcinoma Of Esophagus

Grant support

Our work received funding from the Wellcome Trust (https://wellcome.ac.uk/) the National Institute for Health Research (https://www.nihr.ac.uk/) and Cancer Research UK (http://www.cancerresearchuk.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.