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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,8,4]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Development of preimplantation embryos entails global DNA demethylation on the zygotic genome. The original thought was that TET-deficient embryos would be unlikely to survive early embryogenesis because they would be unable to mediate genome-wide demethylation in the zygote and preimplantation embryo. However, mice lacking the individual TET proteins Tet1, Tet2, or Tet3 have survived until birth and beyond, suggesting redundancy among TET proteins in the early embryogenesis. Here we report that preimplantation embryos doubly disrupted for\n                    <jats:italic>Tet1<\/jats:italic>\n                    and\n                    <jats:italic>Tet3<\/jats:italic>\n                    show abnormal embryonic phenotypes, whose incomplete penetrance correlates with a high variability of transcriptional profiles and DNA methylation status. Our data suggest that in addition to facilitating DNA demethylation, TET proteins and oxidized methylcytosines may regulate the consistency of gene transcription during embryogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1510510112","type":"journal-article","created":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T22:10:15Z","timestamp":1437516615000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":112,"title":["Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis"],"prefix":"10.1073","volume":"112","author":[{"given":"Jinsuk","family":"Kang","sequence":"first","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Lienhard","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, CA 92037;"},{"name":"Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Pastor","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashu","family":"Chawla","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Novotny","sequence":"additional","affiliation":[{"name":"J. Craig Venter Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ageliki","family":"Tsagaratou","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger S.","family":"Lasken","sequence":"additional","affiliation":[{"name":"J. Craig Venter Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Azim","family":"Surani","sequence":"additional","affiliation":[{"name":"Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei B.","family":"Koralov","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundeep","family":"Kalantry","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Chavez","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjana","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, CA 92037;"},{"name":"Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093;"},{"name":"Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093;"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,7,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1126\/science.1170116","article-title":"Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1","volume":"324","author":"Tahiliani M","year":"2009","unstructured":"M Tahiliani, , Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930\u2013935 (2009).","journal-title":"Science"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1126\/science.1210597","article-title":"Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine","volume":"333","author":"Ito S","year":"2011","unstructured":"S Ito, , Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333, 1300\u20131303 (2011).","journal-title":"Science"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1126\/science.1210944","article-title":"Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA","volume":"333","author":"He YF","year":"2011","unstructured":"YF He, , Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. 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