Britton Edward, Rogerson Connor, Mehta Shaveta, Li Yaoyong, Li Xiaodun, Fitzgerald Rebecca C, Ang Yeng S, Sharrocks Andrew D
School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
PLoS Genet. 2017 Aug 31;13(8):e1006879. doi: 10.1371/journal.pgen.1006879. eCollection 2017 Aug.
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.
食管腺癌（OAC）是最常见的十种癌症之一，其发病率正在迅速上升，但生存率却很低。与许多其他常见癌症相比，人们对这种疾病中发生的分子变化了解相对较少。然而，编码染色质重塑酶的基因在OAC中经常发生突变。这与新兴的概念一致，即癌细胞表现出其染色质环境的重编程，这导致其转录谱随后发生变化。在这里，我们使用ATAC-seq来研究在OAC中使用细胞系和患者来源材料发生的染色质变化。我们证明癌细胞的调节染色质环境存在实质性变化，并利用这些数据我们发现了ETS和AP1转录因子在驱动OAC细胞中发现的基因表达变化方面的重要作用。
