Imperial College London
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DrEdCurry

Faculty of Medicine, Department of Surgery & Cancer

Honorary Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 5943e.curry

 
 
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Location

 

Open PlanInstitute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Simmonds:2017:10.1186/s13073-017-0443-z,
author = {Simmonds, P and Loomis, E and Curry, E},
doi = {10.1186/s13073-017-0443-z},
journal = {Genome Medicine},
title = {DNA methylation-based chromatin compartments and ChIP-seq profiles reveal transcriptional drivers of prostate carcinogenesis},
url = {http://dx.doi.org/10.1186/s13073-017-0443-z},
volume = {9},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background – Profiles of DNA methylation of many tissues relevant in human disease have been obtained from microarrays and are publically available. These can be used to generate maps of chromatin compartmentalization, demarcating open and closed chromatin genome-wide. Additionally, large sets of genome-wide transcription factor binding profiles have been made available thanks to ChIP-seq technology.Methods – We have identified genomic regions with altered chromatin compartmentalization in prostate adenocarcinoma tissue relative to normal prostate tissue, using DNA methylation microarray data from The Cancer Genome Atlas. DNA binding profiles from ENCODE ChIP-seq studies have been systematically screened to find transcription factors with inferred DNA-binding sites located in discordantly open/closed chromatin in malignant tissue (compared with non-cancer control tissue). We have combined this with tests for corresponding up-/down-regulation of the transcription factors' putative target genes to obtain an integrated measure of cancer-specific regulatory activity to identify likely transcriptional drivers of prostate cancer.Results – Generally, we find that the degree to which transcription factors preferentially bind regions of chromatin that become more accessible during prostate carcinogenesis is significantly associated to the level of systematic upregulation of their targets, at the level of gene expression.   Our approach has yielded 11 transcription factors that show strong cancer-specific transcriptional activation of targets, including the novel candidates KAT2A and TRIM28, alongside established drivers of prostate cancer MYC, ETS1, GABP and YY1.Conclusions – This approach to integrated epigenetic and transcriptional profiling using publically available data represents a cheap and powerful technique for identifying potential drivers of human disease. In our application to prostate adenocarcinoma data, the fact that well known drivers
AU  - Simmonds,P
AU  - Loomis,E
AU  - Curry,E
DO  - 10.1186/s13073-017-0443-z
PY  - 2017///
SN  - 1756-994X
TI  - DNA methylation-based chromatin compartments and ChIP-seq profiles reveal transcriptional drivers of prostate carcinogenesis
T2  - Genome Medicine
UR  - http://dx.doi.org/10.1186/s13073-017-0443-z
UR  - http://hdl.handle.net/10044/1/48686
VL  - 9
ER  -
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