title: DNA methylation: TET proteins-guardians of CpG islands?
abstract: DNA methylation is involved in key cellular processes, including X-chromosome inactivation, imprinting and transcriptional silencing of specific genes and repetitive elements. DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. The recent discovery that the three members of the TET protein family can convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) has provided a potential mechanism leading to DNA demethylation. Moreover, the demonstration that TET2 is frequently mutated in haematopoietic tumours suggests that the TET proteins are important regulators of cellular identity. Here, we review the current knowledge regarding the function of the TET proteins, and discuss various mechanisms by which they contribute to transcriptional control. We propose that the TET proteins have an important role in regulating DNA methylation fidelity, and that their inactivation contributes to the DNA hypermethylation phenotype often observed in cancer.
authors.affiliation: Biotech Research and Innovation Centre (BRIC), and Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Kristine
authors.initials: K
authors.lastname: Williams
authors.forename: Jesper
authors.initials: J
authors.lastname: Christensen
authors.forename: Kristian
authors.initials: K
authors.lastname: Helin
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism / Q000031:analogs & derivatives; D000818:Animals; D018899:CpG Islands; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine