{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:06:41Z","timestamp":1792822001938,"version":"4.5.0"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"6","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R35 CA210043"],"award-info":[{"award-number":["R35 CA210043"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD016262"],"award-info":[{"award-number":["S10OD016262"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["S10RR027366"],"award-info":[{"award-number":["S10RR027366"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005909","name":"University of California Institute for Mexico and the United States","doi-asserted-by":"publisher","award":["UC MEXUS-CONACYT Fellowship"],"award-info":[{"award-number":["UC MEXUS-CONACYT Fellowship"]}],"id":[{"id":"10.13039\/100005909","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20gm1210003"],"award-info":[{"award-number":["JP20gm1210003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["(A) 20KK0351"],"award-info":[{"award-number":["(A) 20KK0351"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A6A1A03025810"],"award-info":[{"award-number":["2018R1A6A1A03025810"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1F1A1063340"],"award-info":[{"award-number":["2019R1F1A1063340"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002613","name":"Ulsan National Institute of Science and Technology","doi-asserted-by":"publisher","award":["1.180075.01"],"award-info":[{"award-number":["1.180075.01"]}],"id":[{"id":"10.13039\/501100002613","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002613","name":"Ulsan National Institute of Science and Technology","doi-asserted-by":"publisher","award":["1.220023.01"],"award-info":[{"award-number":["1.220023.01"]}],"id":[{"id":"10.13039\/501100002613","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19H05650"],"award-info":[{"award-number":["JP19H05650"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,2,7]]},"abstract":"<jats:p>\n                    The three mammalian TET dioxygenases oxidize the methyl group of 5-methylcytosine in DNA, and the oxidized methylcytosines are essential intermediates in all known pathways of DNA demethylation. To define the in\u00a0vivo consequences of complete TET deficiency, we inducibly deleted all three\n                    <jats:italic>Tet<\/jats:italic>\n                    genes in the mouse genome.\n                    <jats:italic>Tet1\/2\/3-inducible TKO<\/jats:italic>\n                    (\n                    <jats:italic>iTKO<\/jats:italic>\n                    ) mice succumbed to acute myeloid leukemia (AML) by 4 to 5 wk. Single-cell RNA sequencing of\n                    <jats:italic>Tet iTKO<\/jats:italic>\n                    bone marrow cells revealed the appearance of new myeloid cell populations characterized by a striking increase in expression of all members of the\n                    <jats:italic>stefin\/cystatin<\/jats:italic>\n                    gene cluster on mouse chromosome 16. In patients with AML, high\n                    <jats:italic>stefin\/cystatin<\/jats:italic>\n                    gene expression correlates with poor clinical outcomes. Increased expression of the clustered\n                    <jats:italic>stefin\/cystatin<\/jats:italic>\n                    genes was associated with a heterochromatin-to-euchromatin compartment switch with readthrough transcription downstream of the clustered\n                    <jats:italic>stefin\/cystatin<\/jats:italic>\n                    genes as well as other highly expressed genes, but only minor changes in DNA methylation. Our data highlight roles for TET enzymes that are distinct from their established function in DNA demethylation and instead involve increased transcriptional readthrough and changes in three-dimensional genome organization.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2214824120","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T14:01:56Z","timestamp":1675260116000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":17,"title":["Inducible disruption of\n                    <i>Tet<\/i>\n                    genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch"],"prefix":"10.1073","volume":"120","author":[{"given":"Hiroshi","family":"Yuita","sequence":"first","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac F.","family":"L\u00f3pez-Moyado","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA 92037"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7301-7020","authenticated-orcid":false,"given":"Hyeongmin","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur Xiuyuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA 92037"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Scott-Browne","sequence":"additional","affiliation":[{"name":"Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206"},{"name":"Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6678-0121","authenticated-orcid":false,"given":"Jungeun","family":"An","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1434-2007","authenticated-orcid":false,"given":"Toshinori","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"},{"name":"Japan Agency for Medical Research and Development (AMED), Core Research for Evolutional Science and Technology (CREST), Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Onodera","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA 92037"},{"name":"Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"},{"name":"Institute for Advanced Academic Research, Chiba University, Inage-ku, Chiba 263-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myunggon","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea"},{"name":"Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1870-1775","authenticated-orcid":false,"given":"Anjana","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA 92037"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,2]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1170116"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019791475"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1210944"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18290"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aau7523"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.12.023"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.08.016"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.08.026"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.357"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412327111"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2015.10.009"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3148"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.06.001"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.06.003"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019001324"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.10.037"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10071"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008888"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.05.003"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.51"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3777"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0121-4"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)80804-C"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.5044"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2019.05.002"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53610-7"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071679"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0623-z"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301689"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007500"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1903059116"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3630"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.047"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-020-03551-0"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.05.003"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.032"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0125-z"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0060-8"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.11.036"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba5545"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109722"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.001"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0479-7"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23451"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.248005.114"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac642"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10102"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1112317108"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12239"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510510112"},{"key":"e_1_3_4_51_2","unstructured":"Isaac F. L\u00f3pez-Moyado H. Yuita J. Scott-Browne M. Ko Inducible disruption of Tet genes results in myeloid malignancy readthrough transcription and a heterochromatin-to-euchromatin switch. Gene Expression Omnibus (GEO) https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE2227265 Deposited 11 January 2023."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2214824120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T09:15:54Z","timestamp":1695287754000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2214824120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,2,7]]}},"alternative-id":["10.1073\/pnas.2214824120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2214824120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2]]},"assertion":[{"value":"2022-08-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2214824120"}}