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| Status |
Public on Feb 03, 2015 |
| Title |
5-hydroxymethylcytosine marks promoters in colon that resist hypermethylation in cancer [seq] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The discovery of cytosine hydroxymethylation (5-hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behavior in colon cancer. 5-hmC is globally reduced in proliferating cells such as colon tumors and the gut crypt progenitors, from which tumors can arise. Here, we show that colorectal tumors and cancer cells express Ten-Eleven Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5-hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5-hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells. Together our results indicate that promoters that acquire 5-hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5-hmC in tumors. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.
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| Overall design |
5 normal colon samples and 4 matching tumor samples were profiled for 5-hydroxymethylcytosine content genomewide using hmeDIP-seq.
The colorectal cancer cell line HCT116 was profiled for binding of TET2 genomewide by chromatin immunoprecipitation sequencing (ChIP-seq).
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| |
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| Contributor(s) |
Uribe-Lewis S, Stark R, Carroll T, Dunning M, Halim S, Vowler S |
| Citation(s) |
25853800 |
| |
| Submission date |
Jun 03, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Chandra Chilamakuri |
| E-mail(s) |
[email protected]
|
| Organization name |
Cancer Research UK Cambridge Institute
|
| Street address |
Robinson Way
|
| City |
Cambridge |
| ZIP/Postal code |
CB2 0RE |
| Country |
United Kingdom |
| |
|
| Platforms (2) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL15456 |
Illumina HiScanSQ (Homo sapiens) |
|
| Samples (17)
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| This SubSeries is part of SuperSeries: |
| GSE47592 |
5-hydroxymethylcytosine marks promoters in colon that resist hypermethylation in cancer |
|
| Relations |
| BioProject |
PRJNA206436 |
| SRA |
SRP023528 |
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