title: Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in Coprinopsis cinerea.
abstract: 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.
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037;
authors.forename: Lukas
authors.initials: L
authors.lastname: Chavez
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037;
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Pacific Biosciences, Menlo Park, CA 94025;
authors.forename: Khai
authors.initials: K
authors.lastname: Luong
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115;
authors.forename: Suneet
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894;
authors.forename: Lakshminarayan M
authors.initials: LM
authors.lastname: Iyer
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
authors.forename: William A
authors.initials: WA
authors.lastname: Pastor
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Virginia K
authors.initials: VK
authors.lastname: Hench
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Sylvia A
authors.initials: SA
authors.lastname: Frazier-Bowers
authors.affiliation: Skirball Institute, NYU Langone Medical Center, New York University, New York, NY 10016;
authors.forename: Evgenia
authors.initials: E
authors.lastname: Korol
authors.affiliation: Environmental Toxicology Graduate Program and Department of Chemistry, University of California, Riverside, CA 92521; and.
authors.forename: Shuo
authors.initials: S
authors.lastname: Liu
authors.affiliation: Skirball Institute, NYU Langone Medical Center, New York University, New York, NY 10016;
authors.forename: Mamta
authors.initials: M
authors.lastname: Tahiliani
authors.affiliation: Environmental Toxicology Graduate Program and Department of Chemistry, University of California, Riverside, CA 92521; and.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Pacific Biosciences, Menlo Park, CA 94025;
authors.forename: Tyson A
authors.initials: TA
authors.lastname: Clark
authors.affiliation: Pacific Biosciences, Menlo Park, CA 94025;
authors.forename: Jonas
authors.initials: J
authors.lastname: Korlach
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Pukkila
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894;
authors.forename: L
authors.initials: L
authors.lastname: Aravind
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093 arao@liai.org.
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism*; D001487:Basidiomycota / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000235:genetics; D019175:DNA Methylation; D004251:DNA Transposable Elements / Q000235:genetics; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D025301:Hyphae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D010084:Oxidation-Reduction; D017421:Sequence Analysis / Q000379:methods; D013172:Spores, Fungal / Q000254:growth & development / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D005656:Fungal Proteins; D044503:5-Methylcytosine; D049308:Dioxygenases
keywords: 5caC; 5fC; 5mC; SMRT-seq; TET