Dataset Information


Hydroxymethylcytosine in mouse intestinal differentiation [RNA-Seq]

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. Overall design: Four biological replicates were analysed per cell type purified by flow cytometry using the CD24 marker and depletion of CD45 and Ulex lectin positive cells. See Wong et al. NatCellBiol 2012 Mar 4;14(4):401-8 or Buczacki et al. Nature 2013 Mar 7;495(7439):65-9. CD24Mid are also referred to as CD24low in the manuscript.

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Chandra Chilamakuri  

PROVIDER: GSE53190 | GEO | 2017-12-01



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