期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12983
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资金
- Genome Institute of Singapore under the Agency for Science, Technology and Research, Biomedical Research Council Young Investigator Grant [1510851024]
- National Medical Research Council [TCR/009-NUHS/2013, NMRC/STaR/0026/2015]
- Ministry of Education Academic Research Fund (AcRF) Tier 2 [MOE2014-T2-1-138]
- National Research Foundation Singapore [NRF-NRFF2012-054]
- Wellcome Trust [106130/Z/14/Z]
- Medical Research Council (MRC)
- Wellcome Trust Clinical Research Training Fellowship [098931/Z/12/Z]
- Singapore Ministry of Education Academic Research Fund Tier 3
- National Research Foundation Singapore
- Singapore Ministry of Education under its Research Centres of Excellence initiative
- MRC [MC_UU_12009/15, MR/N00969X/1] Funding Source: UKRI
- Wellcome Trust [098931/Z/12/Z] Funding Source: Wellcome Trust
- Medical Research Council [MR/N00969X/1, MC_UU_12009/15] Funding Source: researchfish
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 HNF4 alpha. 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.
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