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Series GSE98012 Query DataSets for GSE98012
Status Public on Jun 12, 2018
Title Enhancer profiling in metastatic cancer [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Metastases cause the majority of cancer-related deaths. Yet, the origins of metastatic cancer phenotypes remain poorly understood. Few metastasis-specific driver mutations have been identified [1-3], raising the possibility that metastatic transcriptional programmes may emerge from perturbations in the oncogenic signalling cascades that support the development of primary tumours. Here, using genome-wide histone modification profiling, high-throughput chromatin conformation capture by Hi-C and functional analysis in human-derived metastasis models of renal and breast cancers, we identify transcriptional enhancers that drive metastatic cancer progression. We demonstrate that specific enhancers and enhancer clusters are activated in metastatic cancer cell populations. The activation status of these enhancers is associated with gene expression patterns predictive of poor patient outcome in clinical samples. CRISPRi-mediated inhibition of enhancer activity and genetic ablation of enhancer sequences demonstrated the requirement of metastasis-associated regulatory elements for metastatic colonization in vivo. We further show that metastatic cancer clones co-opt evolutionarily conserved enhancers that converge on shared metastasis driver genes, such as CXCR4. Thus, we provide functional evidence for the requirement of specific enhancers for metastatic colonization and show that metastatic traits can arise through tissue-specific commissioning of distal gene regulatory elements.
Overall design Examination of 2 different histone modifications and transcription factors in experimental model systems of metastasis.
Contributor(s) Rodrigues P, Vanharanta S
Citation(s) 29875134
Submission date Apr 20, 2017
Last update date May 15, 2019
Contact name Sakari Vanharanta
Organization name University of Cambridge
Department MRC Cancer Unit
Lab Vanharanta
Street address Box 197, Cambridge Biomedical Campus
City Cambridge
ZIP/Postal code CB2 0XZ
Country United Kingdom
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (44)
GSM2585456 ChIP-Seq_1833-BoM_H3K27ac
GSM2585457 ChIP-Seq_4175-LM2_H3K27ac
GSM2585458 ChIP-Seq_786-M1A-Ctrl_H3K27ac
This SubSeries is part of SuperSeries:
GSE98015 Enhancer profiling in metastatic cancer
BioProject PRJNA383670
SRA SRP104404

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE98012_RAW.tar 48.6 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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