Transcriptomics

Dataset Information

3

5-hydroxymethylcytosine marks promoters in colon that resist hypermethylation in cancer [Methylation450 Array]


ABSTRACT: 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. Six samples were analyzed. 2 biological replicates each of HCT116 cells stably transfected with an empty vector control (TET_KD_Plk), with shRNA to TET2 (TET_KD_2C) and with shRNA to TET2 and TET3 (TET_KD_2.3)

ORGANISM(S): Homo sapiens  

SUBMITTER: Matthieu Defrance   Silvia Halim  Santago Uribe-Lewis 

PROVIDER: E-GEOD-63421 | ArrayExpress | 2015-02-03

SECONDARY ACCESSION(S): GSE63421PRJNA267708

REPOSITORIES: GEO, ArrayExpress

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Publications

A comprehensive overview of Infinium HumanMethylation450 data processing.

Dedeurwaerder Sarah S   Defrance Matthieu M   Bizet Martin M   Calonne Emilie E   Bontempi Gianluca G   Fuks François F  

Briefings in bioinformatics 20130829 6


Infinium HumanMethylation450 beadarray is a popular technology to explore DNA methylomes in health and disease, and there is a current explosion in the use of this technique. Despite experience acquired from gene expression microarrays, analyzing Infinium Methylation arrays appeared more complex than initially thought and several difficulties have been encountered, as those arrays display specific features that need to be taken into consideration during data processing. Here, we review several i  ...[more]

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