Please use this identifier to cite or link to this item:
https://doi.org/10.1186/s13073-021-00970-3
DC Field | Value | |
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dc.title | Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer | |
dc.contributor.author | Sheng, Taotao | |
dc.contributor.author | Ho, Shamaine Wei Ting | |
dc.contributor.author | Ooi, Wen Fong | |
dc.contributor.author | Xu, Chang | |
dc.contributor.author | Xing, Manjie | |
dc.contributor.author | Padmanabhan, Nisha | |
dc.contributor.author | Huang, Kie Kyon | |
dc.contributor.author | Ma, Lijia | |
dc.contributor.author | Ray, Mohana | |
dc.contributor.author | Guo, Yu Amanda | |
dc.contributor.author | Sim, Ngak Leng | |
dc.contributor.author | Anene-Nzelu, Chukwuemeka George | |
dc.contributor.author | Chang, Mei Mei | |
dc.contributor.author | Razavi-Mohseni, Milad | |
dc.contributor.author | Beer, Michael A | |
dc.contributor.author | Foo, Roger Sik Yin | |
dc.contributor.author | Sundar, Raghav | |
dc.contributor.author | Chan, Yiong Huak | |
dc.contributor.author | Tan, Angie Lay Keng | |
dc.contributor.author | Ong, Xuewen | |
dc.contributor.author | Skanderup, Anders Jacobsen | |
dc.contributor.author | White, Kevin P | |
dc.contributor.author | Jha, Sudhakar | |
dc.contributor.author | Tan, Patrick | |
dc.date.accessioned | 2021-11-11T07:41:58Z | |
dc.date.available | 2021-11-11T07:41:58Z | |
dc.date.issued | 2021-10-11 | |
dc.identifier.citation | Sheng, Taotao, Ho, Shamaine Wei Ting, Ooi, Wen Fong, Xu, Chang, Xing, Manjie, Padmanabhan, Nisha, Huang, Kie Kyon, Ma, Lijia, Ray, Mohana, Guo, Yu Amanda, Sim, Ngak Leng, Anene-Nzelu, Chukwuemeka George, Chang, Mei Mei, Razavi-Mohseni, Milad, Beer, Michael A, Foo, Roger Sik Yin, Sundar, Raghav, Chan, Yiong Huak, Tan, Angie Lay Keng, Ong, Xuewen, Skanderup, Anders Jacobsen, White, Kevin P, Jha, Sudhakar, Tan, Patrick (2021-10-11). Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer. GENOME MEDICINE 13 (1). ScholarBank@NUS Repository. https://doi.org/10.1186/s13073-021-00970-3 | |
dc.identifier.issn | 1756994X | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/205937 | |
dc.description.abstract | Background: Enhancers are distal cis-regulatory elements required for cell-specific gene expression and cell fate determination. In cancer, enhancer variation has been proposed as a major cause of inter-patient heterogeneity—however, most predicted enhancer regions remain to be functionally tested. Methods: We analyzed 132 epigenomic histone modification profiles of 18 primary gastric cancer (GC) samples, 18 normal gastric tissues, and 28 GC cell lines using Nano-ChIP-seq technology. We applied Capture-based Self-Transcribing Active Regulatory Region sequencing (CapSTARR-seq) to assess functional enhancer activity. An Activity-by-contact (ABC) model was employed to explore the effects of histone acetylation and CapSTARR-seq levels on enhancer-promoter interactions. Results: We report a comprehensive catalog of 75,730 recurrent predicted enhancers, the majority of which are GC-associated in vivo (> 50,000) and associated with lower somatic mutation rates inferred by whole-genome sequencing. Applying CapSTARR-seq to the enhancer catalog, we observed significant correlations between CapSTARR-seq functional activity and H3K27ac/H3K4me1 levels. Super-enhancer regions exhibited increased CapSTARR-seq signals compared to regular enhancers, even when decoupled from native chromatin contexture. We show that combining histone modification and CapSTARR-seq functional enhancer data improves the prediction of enhancer-promoter interactions and pinpointing of germline single nucleotide polymorphisms (SNPs), somatic copy number alterations (SCNAs), and trans-acting TFs involved in GC expression. We identified cancer-relevant genes (ING1, ARL4C) whose expression between patients is influenced by enhancer differences in genomic copy number and germline SNPs, and HNF4α as a master trans-acting factor associated with GC enhancer heterogeneity. Conclusions: Our results indicate that combining histone modification and functional assay data may provide a more accurate metric to assess enhancer activity than either platform individually, providing insights into the relative contribution of genetic (cis) and regulatory (trans) mechanisms to GC enhancer functional heterogeneity. | |
dc.language.iso | en | |
dc.publisher | BMC | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Genetics & Heredity | |
dc.subject | Enhancer landscape | |
dc.subject | Gastric cancer | |
dc.subject | CapSTARR-seq | |
dc.subject | Enhancer-promoter interactions | |
dc.subject | Enhancer heterogeneity | |
dc.subject | SUPER-ENHANCERS | |
dc.subject | CELL IDENTITY | |
dc.subject | GENE | |
dc.subject | EXPRESSION | |
dc.subject | IDENTIFICATION | |
dc.subject | DISEASE | |
dc.subject | POLYMORPHISMS | |
dc.subject | ARCHITECTURE | |
dc.subject | ANNOTATION | |
dc.subject | PROMOTERS | |
dc.type | Article | |
dc.date.updated | 2021-11-09T21:24:17Z | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1186/s13073-021-00970-3 | |
dc.description.sourcetitle | GENOME MEDICINE | |
dc.description.volume | 13 | |
dc.description.issue | 1 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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