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July 7, 2019  |  

Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in Coprinopsis cinerea.

Authors: Chavez, Lukas and Huang, Yun and Luong, Khai and Agarwal, Suneet and Iyer, Lakshminarayan M and Pastor, William A and Hench, Virginia K and Frazier-Bowers, Sylvia A and Korol, Evgenia and Liu, Shuo and Tahiliani, Mamta and Wang, Yinsheng and Clark, Tyson A and Korlach, Jonas and Pukkila, Patricia J and Aravind, L and Rao, Anjana

TET/JBP enzymes oxidize 5-methylpyrimidines in DNA. In mammals, the oxidized methylcytosines (oxi-mCs) function as epigenetic marks and likely intermediates in DNA demethylation. Here we present a method based on diglucosylation of 5-hydroxymethylcytosine (5hmC) to simultaneously map 5hmC, 5-formylcytosine, and 5-carboxylcytosine at near-base-pair resolution. We have used the method to map the distribution of oxi-mC across the genome of Coprinopsis cinerea, a basidiomycete that encodes 47 TET/JBP paralogs in a previously unidentified class of DNA transposons. Like 5-methylcytosine residues from which they are derived, oxi-mC modifications are enriched at centromeres, TET/JBP transposons, and multicopy paralogous genes that are not expressed, but rarely mark genes whose expression changes between two developmental stages. Our study provides evidence for the emergence of an epigenetic regulatory system through recruitment of selfish elements in a eukaryotic lineage, and describes a method to map all three different species of oxi-mCs simultaneously.

Journal: Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.1419513111
Year: 2014

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