title: 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer.
abstract: BACKGROUND
  The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced in proliferating cells such as colon tumours and the gut crypt progenitors, from which tumours can arise.
  
  
  RESULTS
  Here, we show that colorectal tumours and cancer cells express Ten-Eleven-Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5hmC 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 5hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells.
  
  
  CONCLUSIONS
  Together our results indicate that promoters that acquire 5hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC in tumours. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.
authors: Santiago
authors: S
authors: Uribe-Lewis
authors: Rory
authors: R
authors: Stark
authors: Thomas
authors: T
authors: Carroll
authors: Mark J
authors: MJ
authors: Dunning
authors: Martin
authors: M
authors: Bachman
authors: Yoko
authors: Y
authors: Ito
authors: Lovorka
authors: L
authors: Stojic
authors: Silvia
authors: S
authors: Halim
authors: Sarah L
authors: SL
authors: Vowler
authors: Andy G
authors: AG
authors: Lynch
authors: Benjamin
authors: B
authors: Delatte
authors: Eric J
authors: EJ
authors: de Bony
authors: Laurence
authors: L
authors: Colin
authors: Matthieu
authors: M
authors: Defrance
authors: Felix
authors: F
authors: Krueger
authors: Ana-Luisa
authors: AL
authors: Silva
authors: Rogier
authors: R
authors: Ten Hoopen
authors: Ashraf Ek
authors: AE
authors: Ibrahim
authors: François
authors: F
authors: Fuks
authors: Adele
authors: A
authors: Murrell
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D049109:Cell Proliferation / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D049308:Dioxygenases; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D049308:Dioxygenases; C541081:TET2 protein, human