Role of TET enzymes in DNA methylation, development, and cancer

Genes Dev. 2016 Apr 1;30(7):733-50. doi: 10.1101/gad.276568.115.

Abstract

The pattern of DNA methylation at cytosine bases in the genome is tightly linked to gene expression, and DNA methylation abnormalities are often observed in diseases. The ten eleven translocation (TET) enzymes oxidize 5-methylcytosines (5mCs) and promote locus-specific reversal of DNA methylation. TET genes, and especially TET2, are frequently mutated in various cancers, but how the TET proteins contribute to prevent the onset and maintenance of these malignancies is largely unknown. Here, we highlight recent advances in understanding the physiological function of the TET proteins and their role in regulating DNA methylation and transcription. In addition, we discuss some of the key outstanding questions in the field.

Keywords: DNA demethylation; DNA methylation; TET; hydroxymethyl cytosine; hematopoiesis; leukemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytosine / metabolism
  • DNA Methylation / physiology*
  • DNA-Binding Proteins / metabolism
  • Dioxygenases / genetics
  • Dioxygenases / metabolism*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Oxidation-Reduction
  • Proto-Oncogene Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Cytosine
  • Dioxygenases
  • TET2 protein, human