Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity
| Autor: | Chang Xu, Weng Hoong Chan, Patrick Tan, Mei Chee Lim, Muhammad Khairul Ramlee, Shang Li, James Qu Zhengzhong, Joyce Lin Suling, Aditi Qamra, James O.J. Davies, Ai Ping Lee-Lim, Melissa J. Fullwood, Steve Rozen, Wen Fong Ooi, Ming Hui Lee, Khee Chee Soo, Tannistha Nandi, Yang Sun Chan, Chow Yin Wong, Su Ting Tay, Jianjun Liu, Pierce K. H. Chow, Kevin Lim, Deepak Babu, Sun Young Rha, Axel M. Hillmer, Bin Tean Teh, Jim R. Hughes, Lai Fong Poon, Manjie Xing, Fan Cao, Xiaosai Yao, Astrid Irwanto, Wai-Keong Wong, Hock Soo Ong |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetics Multidisciplinary Somatic cell Science General Physics and Astronomy General Chemistry Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Article 3. Good health Chromatin 03 medical and health sciences 030104 developmental biology Super-enhancer medicine Cancer research Epigenetics Enhancer Carcinogenesis Transcription factor Epigenomics |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-17 (2016) |
| ISSN: | 2041-1723 |
| Popis: | Regulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastric tissues and cell lines, we highlight 36,973 predicted enhancers and 3,759 predicted super-enhancers respectively. Cell-line-defined super-enhancers can be subclassified by their somatic alteration status into somatic gain, loss and unaltered categories, each displaying distinct epigenetic, transcriptional and pathway enrichments. Somatic gain super-enhancers are associated with complex chromatin interaction profiles, expression patterns correlated with patient outcome and dense co-occupancy of the transcription factors CDX2 and HNF4α. Somatic super-enhancers are also enriched in genetic risk SNPs associated with cancer predisposition. Our results reveal a genome-wide reprogramming of the GC enhancer and super-enhancer landscape during tumorigenesis, contributing to dysregulated local and regional cancer gene expression. Gene expression is regulated by enhancers and super-enhancers, which can be identified by chromatin profiling. Here, the authors surveyed gastric cancer samples and cell lines to identify enhancer elements exhibiting somatic alterations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|