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

被引:31
作者
Britton, Edward [1 ]
Rogerson, Connor [1 ]
Mehta, Shaveta [2 ,3 ]
Li, Yaoyong [1 ]
Li, Xiaodun [4 ]
Fitzgerald, Rebecca C. [4 ]
Ang, Yeng S. [2 ,5 ]
Sharrocks, Andrew D. [1 ,4 ,5 ]
机构
[1] Univ Manchester, Sch Biol Sci, Fac Biol Med & Hlth, Manchester, Lancs, England
[2] Univ Manchester, Sch Med Sci, Fac Biol Med & Hlth, Manchester, Lancs, England
[3] Christie Hosp, Manchester, Lancs, England
[4] Univ Cambridge, MRC Canc Unit, Hutchison MRC Res Ctr, Cambridge, England
[5] Univ Manchester, GI Sci Ctr, Salford Royal NHS FT, Stott Lane, Salford, Lancs, England
来源
PLOS GENETICS | 2017年 / 13卷 / 08期
基金
英国惠康基金;
关键词
DNA-BINDING; BARRETTS-ESOPHAGUS; PROTEIN-1; AP1; IN-VITRO; C-JUN; ETS; ACTIVATION; DIFFERENTIATION; COOPERATE; SUBFAMILY;
D O I
10.1371/journal.pgen.1006879
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页数:24
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