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

Autor: Britton E; School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom., Rogerson C; School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom., Mehta S; School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.; Christie Hospital, Manchester, United Kingdom., Li Y; School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom., Li X; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom., Fitzgerald RC; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom., Ang YS; School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.; GI Science Centre, Salford Royal NHS FT, University of Manchester, Stott Lane, Salford, United Kingdom., Sharrocks AD; School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom.; GI Science Centre, Salford Royal NHS FT, University of Manchester, Stott Lane, Salford, United Kingdom.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2017 Aug 31; Vol. 13 (8), pp. e1006879. Date of Electronic Publication: 2017 Aug 31 (Print Publication: 2017).
DOI: 10.1371/journal.pgen.1006879
Abstrakt: 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.
Databáze: MEDLINE