Abstract：
:TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation. Abnormal gains of DNAm and 5hmC occur simultaneously in OS, and knocking down TET2 dynamically alters this balance by enhancing 5mC and reducing 5hmC. TET2 reduction results in hypermethylation of promoter CGIs and enhancers in loci largely overlapping with those induced by OS. Thus, TET2 indeed may protect against abnormal, cancer DNAm in a manner linked to DNA damage.
journal_name
Mol Celljournal_title
Molecular cellauthors
Zhang YW,Wang Z,Xie W,Cai Y,Xia L,Easwaran H,Luo J,Yen RC,Li Y,Baylin SBdoi
10.1016/j.molcel.2016.12.013subject
Has Abstractpub_date
2017-01-19 00:00:00pages
323-335issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(16)30851-6journal_volume
65pub_type
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