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| Status |
Public on Jun 12, 2018 |
| Title |
Enhancer profiling in metastatic cancer [HiC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| 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.
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| |
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| Overall design |
Examination of chromatin conformation by HiC in experimental model systems of metastasis.
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| Contributor(s) |
Harewood L, Olan I, Rodrigues P, Samarajiwa SA, Vanharanta S |
| Citation(s) |
29875134 |
| Submission date |
May 18, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Sakari Vanharanta |
| E-mail(s) |
sakari.vanharanta@helsinki.fi
|
| Organization name |
University of Helsinki
|
| Department |
Translational Cancer Medicine Program
|
| Lab |
Vanharanta
|
| Street address |
Haartmaninkatu 8
|
| City |
Helsinki |
| ZIP/Postal code |
00014 |
| Country |
Finland |
| |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE98015 |
Enhancer profiling in metastatic cancer |
|
| Relations |
| BioProject |
PRJNA387149 |
| SRA |
SRP107308 |
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