{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:17:59Z","timestamp":1790842679793,"version":"4.1.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"8035","license":[{"start":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:00:00Z","timestamp":1727827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:00:00Z","timestamp":1727827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2024,10,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mutation of tet methylcytosine dioxygenase 2 (encoded by\n                    <jats:italic>TET2<\/jats:italic>\n                    ) drives myeloid malignancy initiation and progression\n                    <jats:sup>1\u20133<\/jats:sup>\n                    . TET2 deficiency is known to cause a globally opened chromatin state and activation of genes contributing to aberrant haematopoietic stem cell self-renewal\n                    <jats:sup>4,5<\/jats:sup>\n                    . However, the open chromatin observed in TET2-deficient mouse embryonic stem cells, leukaemic cells and haematopoietic stem and progenitor cells\n                    <jats:sup>5<\/jats:sup>\n                    is inconsistent with the designated role of DNA 5-methylcytosine oxidation of TET2. Here we show that chromatin-associated retrotransposon RNA 5-methylcytosine (m\n                    <jats:sup>5<\/jats:sup>\n                    C) can be recognized by the methyl-CpG-binding-domain protein MBD6, which guides deubiquitination of nearby monoubiquitinated Lys119 of histone H2A (H2AK119ub) to promote an open chromatin state. TET2 oxidizes m\n                    <jats:sup>5<\/jats:sup>\n                    C and antagonizes this MBD6-dependent H2AK119ub deubiquitination. TET2 depletion thereby leads to globally decreased H2AK119ub, more open chromatin and increased transcription in stem cells.\n                    <jats:italic>TET2-<\/jats:italic>\n                    mutant human leukaemia becomes dependent on this gene activation pathway, with\n                    <jats:italic>MBD6<\/jats:italic>\n                    depletion selectively blocking proliferation of\n                    <jats:italic>TET2<\/jats:italic>\n                    -mutant leukaemic cells and largely reversing the haematopoiesis defects caused by\n                    <jats:italic>Tet2<\/jats:italic>\n                    loss in mouse models. Together, our findings reveal a chromatin regulation pathway by TET2 through retrotransposon RNA m\n                    <jats:sup>5<\/jats:sup>\n                    C oxidation and identify the downstream MBD6 protein as a feasible target for developing therapies specific against\n                    <jats:italic>TET2<\/jats:italic>\n                    mutant malignancies.\n                  <\/jats:p>","DOI":"10.1038\/s41586-024-07969-x","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T12:02:30Z","timestamp":1727870550000},"page":"986-994","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["RNA m5C oxidation by TET2 regulates chromatin state and leukaemogenesis"],"prefix":"10.1038","volume":"634","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7152-5435","authenticated-orcid":false,"given":"Zhongyu","family":"Zou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3308-906X","authenticated-orcid":false,"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4900-506X","authenticated-orcid":false,"given":"Zijie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6956-1450","authenticated-orcid":false,"given":"Boyang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiding","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7849-976X","authenticated-orcid":false,"given":"Chenxi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinzhe","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianbin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juyeong","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8578-1568","authenticated-orcid":false,"given":"Qing","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8524-4095","authenticated-orcid":false,"given":"Feng-Chun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7063-6253","authenticated-orcid":false,"given":"Mingjiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4319-7424","authenticated-orcid":false,"given":"Chuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,2]]},"reference":[{"key":"7969_CR1","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1056\/NEJMc091348","volume":"361","author":"A Tefferi","year":"2009","unstructured":"Tefferi, A., Lim, K. H. & Levine, R. Mutation in TET2 in myeloid cancers. N. Engl. J. Med. 361, 1117 (2009).","journal-title":"N. Engl. J. Med."},{"key":"7969_CR2","doi-asserted-by":"publisher","first-page":"6403","DOI":"10.1182\/blood-2009-02-205690","volume":"113","author":"AM Jankowska","year":"2009","unstructured":"Jankowska, A. M. et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic\/myeloproliferative neoplasms. Blood 113, 6403\u20136410 (2009).","journal-title":"Blood"},{"key":"7969_CR3","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1038\/ng.391","volume":"41","author":"SM Langemeijer","year":"2009","unstructured":"Langemeijer, S. M. et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat. Genet. 41, 838\u2013842 (2009).","journal-title":"Nat. Genet."},{"key":"7969_CR4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.ccr.2011.06.001","volume":"20","author":"K Moran-Crusio","year":"2011","unstructured":"Moran-Crusio, K. et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20, 11\u201324 (2011).","journal-title":"Cancer Cell"},{"key":"7969_CR5","doi-asserted-by":"publisher","first-page":"16933","DOI":"10.1073\/pnas.1903059116","volume":"116","author":"IF Lopez-Moyado","year":"2019","unstructured":"Lopez-Moyado, I. F. et al. Paradoxical association of TET loss of function with genome-wide DNA hypomethylation. Proc. Natl Acad. Sci. USA 116, 16933\u201316942 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"7969_CR6","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/s41586-018-0350-5","volume":"559","author":"D Wu","year":"2018","unstructured":"Wu, D. et al. Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature 559, 637\u2013641 (2018).","journal-title":"Nature"},{"key":"7969_CR7","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/nature10443","volume":"477","author":"TP Gu","year":"2011","unstructured":"Gu, T. P. et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477, 606\u2013610 (2011).","journal-title":"Nature"},{"key":"7969_CR8","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.tig.2014.07.005","volume":"30","author":"Y Huang","year":"2014","unstructured":"Huang, Y. & Rao, A. Connections between TET proteins and aberrant DNA modification in cancer. Trends Genet. 30, 464\u2013474 (2014).","journal-title":"Trends Genet."},{"key":"7969_CR9","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.ccr.2010.11.015","volume":"18","author":"ME Figueroa","year":"2010","unstructured":"Figueroa, M. E. et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18, 553\u2013567 (2010).","journal-title":"Cancer Cell"},{"key":"7969_CR10","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.1056\/NEJMoa0810069","volume":"360","author":"F Delhommeau","year":"2009","unstructured":"Delhommeau, F. et al. Mutation in TET2 in myeloid cancers. N. Engl. J. Med. 360, 2289\u20132301 (2009).","journal-title":"N. Engl. J. Med."},{"key":"7969_CR11","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.ccr.2010.01.020","volume":"17","author":"PS Ward","year":"2010","unstructured":"Ward, P. S. et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17, 225\u2013234 (2010).","journal-title":"Cancer Cell"},{"key":"7969_CR12","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/nature12052","volume":"497","author":"M Ko","year":"2013","unstructured":"Ko, M. et al. Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX. Nature 497, 122\u2013126 (2013).","journal-title":"Nature"},{"key":"7969_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2022.102770","volume":"61","author":"A Abou-Jaoude","year":"2022","unstructured":"Abou-Jaoude, A. et al. Idax and Rinf facilitate expression of Tet enzymes to promote neural and suppress trophectodermal programs during differentiation of embryonic stem cells. Stem Cell Res. 61, 102770 (2022).","journal-title":"Stem Cell Res."},{"key":"7969_CR14","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1016\/j.celrep.2019.07.080","volume":"28","author":"M Ravichandran","year":"2019","unstructured":"Ravichandran, M. et al. Rinf regulates pluripotency network genes and Tet enzymes in embryonic stem cells. Cell Rep. 28, 1993\u20132003 (2019).","journal-title":"Cell Rep."},{"key":"7969_CR15","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nrm3589","volume":"14","author":"WA Pastor","year":"2013","unstructured":"Pastor, W. A., Aravind, L. & Rao, A. TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat. Rev. Mol. Cell Biol. 14, 341\u2013356 (2013).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"7969_CR16","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/s41588-018-0060-9","volume":"50","author":"D Guallar","year":"2018","unstructured":"Guallar, D. et al. RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nat. Genet. 50, 443\u2013451 (2018).","journal-title":"Nat. Genet."},{"key":"7969_CR17","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1126\/science.aac5253","volume":"351","author":"B Delatte","year":"2016","unstructured":"Delatte, B. et al. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine. Science 351, 282\u2013285 (2016).","journal-title":"Science"},{"key":"7969_CR18","doi-asserted-by":"publisher","first-page":"11582","DOI":"10.1021\/ja505305z","volume":"136","author":"L Fu","year":"2014","unstructured":"Fu, L. et al. Tet-mediated formation of 5-hydroxymethylcytosine in RNA. J. Am. Chem. Soc. 136, 11582\u201311585 (2014).","journal-title":"J. Am. Chem. Soc."},{"key":"7969_CR19","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nature25434","volume":"554","author":"Q Shen","year":"2018","unstructured":"Shen, Q. et al. Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation. Nature 554, 123\u2013127 (2018).","journal-title":"Nature"},{"key":"7969_CR20","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1016\/j.stem.2023.07.001","volume":"30","author":"Y Li","year":"2023","unstructured":"Li, Y. et al. TET2-mediated mRNA demethylation regulates leukemia stem cell homing and self-renewal. Cell Stem Cell 30, 1072\u20131090 (2023).","journal-title":"Cell Stem Cell"},{"key":"7969_CR21","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1126\/science.aay6018","volume":"367","author":"J Liu","year":"2020","unstructured":"Liu, J. et al. N6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science 367, 580\u2013586 (2020).","journal-title":"Science"},{"key":"7969_CR22","doi-asserted-by":"crossref","unstructured":"Wei, J. et al. FTO mediates LINE1 m6A demethylation and chromatin regulation in mESCs and mouse development. Science 376, 968\u2013973 (2022).","DOI":"10.1126\/science.abe9582"},{"key":"7969_CR23","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/s41586-021-03210-1","volume":"591","author":"W Xu","year":"2021","unstructured":"Xu, W. et al. METTL3 regulates heterochromatin in mouse embryonic stem cells. Nature 591, 317\u2013321 (2021).","journal-title":"Nature"},{"key":"7969_CR24","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/s41586-021-03313-9","volume":"591","author":"J Liu","year":"2021","unstructured":"Liu, J. et al. The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity. Nature 591, 322\u2013326 (2021).","journal-title":"Nature"},{"key":"7969_CR25","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41586-020-03135-1","volume":"591","author":"T Chelmicki","year":"2021","unstructured":"Chelmicki, T. et al. m6A RNA methylation regulates the fate of endogenous retroviruses. Nature 591, 312\u2013316 (2021).","journal-title":"Nature"},{"key":"7969_CR26","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.molcel.2014.08.026","volume":"56","author":"GC Hon","year":"2014","unstructured":"Hon, G. C. et al. 5mC oxidation by Tet2 modulates enhancer activity and timing of transcriptome reprogramming during differentiation. Mol. Cell 56, 286\u2013297 (2014).","journal-title":"Mol. Cell"},{"key":"7969_CR27","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1126\/science.1170116","volume":"324","author":"M Tahiliani","year":"2009","unstructured":"Tahiliani, M. et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930\u2013935 (2009).","journal-title":"Science"},{"key":"7969_CR28","doi-asserted-by":"publisher","unstructured":"Dai, Q. et al. Ultrafast bisulfite sequencing detection of 5-methylcytosine in DNA and RNA. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-023-02034-w (2024).","DOI":"10.1038\/s41587-023-02034-w"},{"key":"7969_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16722-7","volume":"11","author":"H Chen","year":"2020","unstructured":"Chen, H. et al. m5C modification of mRNA serves a DNA damage code to promote homologous recombination. Nat. Commun. 11, 2834 (2020).","journal-title":"Nat. Commun."},{"key":"7969_CR30","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/cr.2017.55","volume":"27","author":"X Yang","year":"2017","unstructured":"Yang, X. et al. 5-methylcytosine promotes mRNA export\u2014NSUN2 as the methyltransferase and ALYREF as an m5C reader. Cell Res. 27, 606\u2013625 (2017).","journal-title":"Cell Res."},{"key":"7969_CR31","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/nature15252","volume":"525","author":"Q Zhang","year":"2015","unstructured":"Zhang, Q. et al. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 525, 389\u2013393 (2015).","journal-title":"Nature"},{"key":"7969_CR32","doi-asserted-by":"publisher","first-page":"3621","DOI":"10.1073\/pnas.1910702117","volume":"117","author":"AK Singh","year":"2020","unstructured":"Singh, A. K. et al. Selective targeting of TET catalytic domain promotes somatic cell reprogramming. Proc. Natl Acad. Sci. USA 117, 3621\u20133626 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"7969_CR33","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/nature02985","volume":"431","author":"H Wang","year":"2004","unstructured":"Wang, H. et al. Role of histone H2A ubiquitination in Polycomb silencing. Nature 431, 873\u2013878 (2004).","journal-title":"Nature"},{"key":"7969_CR34","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.devcel.2004.10.005","volume":"7","author":"M de Napoles","year":"2004","unstructured":"de Napoles, M. et al. Polycomb group proteins Ring1A\/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev. Cell 7, 663\u2013676 (2004).","journal-title":"Dev. Cell"},{"key":"7969_CR35","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nature08966","volume":"465","author":"JC Scheuermann","year":"2010","unstructured":"Scheuermann, J. C. et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465, 243\u2013247 (2010).","journal-title":"Nature"},{"key":"7969_CR36","doi-asserted-by":"publisher","first-page":"28643","DOI":"10.1074\/jbc.M115.661553","volume":"290","author":"S Daou","year":"2015","unstructured":"Daou, S. et al. The BAP1\/ASXL2 histone H2A deubiquitinase complex regulates cell proliferation and is disrupted in cancer. J. Biol. Chem. 290, 28643\u201328663 (2015).","journal-title":"J. Biol. Chem."},{"key":"7969_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13661","volume":"7","author":"S Cooper","year":"2016","unstructured":"Cooper, S. et al. Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2. Nat. Commun. 7, 13661 (2016).","journal-title":"Nat. Commun."},{"key":"7969_CR38","doi-asserted-by":"publisher","first-page":"e11982","DOI":"10.1371\/journal.pone.0011982","volume":"5","author":"S Laget","year":"2010","unstructured":"Laget, S. et al. The human proteins MBD5 and MBD6 associate with heterochromatin but they do not bind methylated DNA. PLoS ONE 5, e11982 (2010).","journal-title":"PLoS ONE"},{"key":"7969_CR39","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1002\/pmic.201400013","volume":"14","author":"HI Baymaz","year":"2014","unstructured":"Baymaz, H. I. et al. MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG-binding domain. Proteomics 14, 2179\u20132189 (2014).","journal-title":"Proteomics"},{"key":"7969_CR40","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-022-02776-x","volume":"23","author":"N Tsuboyama","year":"2022","unstructured":"Tsuboyama, N., Szczepanski, A. P., Zhao, Z. & Wang, L. MBD5 and MBD6 stabilize the BAP1 complex and promote BAP1-dependent cancer. Genome Biol. 23, 206 (2022).","journal-title":"Genome Biol."},{"key":"7969_CR41","doi-asserted-by":"publisher","first-page":"4509","DOI":"10.1182\/blood-2010-12-325241","volume":"118","author":"Z Li","year":"2011","unstructured":"Li, Z. et al. Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood 118, 4509\u20134518 (2011).","journal-title":"Blood"},{"key":"7969_CR42","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nchembio.2250","volume":"13","author":"MY Liu","year":"2017","unstructured":"Liu, M. Y. et al. Mutations along a TET2 active site scaffold stall oxidation at 5-hydroxymethylcytosine. Nat. Chem. Biol. 13, 181\u2013187 (2017).","journal-title":"Nat. Chem. Biol."},{"key":"7969_CR43","doi-asserted-by":"publisher","first-page":"e0135259","DOI":"10.1371\/journal.pone.0135259","volume":"10","author":"YX Liu","year":"2015","unstructured":"Liu, Y. X. et al. Promotion of erythropoietic differentiation in hematopoietic stem cells by SOCS3 knock-down. PLoS ONE 10, e0135259 (2015).","journal-title":"PLoS ONE"},{"key":"7969_CR44","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1002\/stem.1050","volume":"30","author":"C Zhao","year":"2012","unstructured":"Zhao, C. et al. Noncanonical NF-\u03baB signaling regulates hematopoietic stem cell self-renewal and microenvironment interactions. Stem Cells 30, 709\u2013718 (2012).","journal-title":"Stem Cells"},{"key":"7969_CR45","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.3324\/haematol.2018.188466","volume":"103","author":"MS Talkhoncheh","year":"2018","unstructured":"Talkhoncheh, M. S. et al. Transient inhibition of NF-\u03baB signaling enhances ex vivo propagation of human hematopoietic stem cells. Haematologica 103, 1444\u20131450 (2018).","journal-title":"Haematologica"},{"key":"7969_CR46","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1038\/s41556-023-01213-w","volume":"25","author":"X Dou","year":"2023","unstructured":"Dou, X. et al. RBFOX2 recognizes N6-methyladenosine to suppress transcription and block myeloid leukaemia differentiation. Nat. Cell Biol. 25, 1359\u20131368 (2023).","journal-title":"Nat. Cell Biol."},{"key":"7969_CR47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2321611121","volume":"121","author":"R Wu","year":"2024","unstructured":"Wu, R. et al. NSUN5\/TET2-directed chromatin-associated RNA modification of 5-methylcytosine to 5-hydroxymethylcytosine governs glioma immune evasion. Proc. Natl Acad. Sci. USA 121, e2321611121 (2024).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"7969_CR48","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.stem.2013.05.006","volume":"13","author":"RR Zhang","year":"2013","unstructured":"Zhang, R. R. et al. Tet1 regulates adult hippocampal neurogenesis and cognition. Cell Stem Cell 13, 237\u2013245 (2013).","journal-title":"Cell Stem Cell"},{"key":"7969_CR49","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1158\/2643-3230.BCD-20-0173","volume":"2","author":"Y Guan","year":"2021","unstructured":"Guan, Y. et al. A therapeutic strategy for preferential targeting of TET2 mutant and TET-dioxygenase deficient cells in myeloid neoplasms. Blood Cancer Discov. 2, 146\u2013161 (2021).","journal-title":"Blood Cancer Discov."},{"key":"7969_CR50","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/nmeth.4031","volume":"13","author":"X Chen","year":"2016","unstructured":"Chen, X. et al. ATAC-see reveals the accessible genome by transposase-mediated imaging and sequencing. Nat. Methods 13, 1013\u20131020 (2016).","journal-title":"Nat. Methods"},{"key":"7969_CR51","first-page":"7219","volume":"14","author":"J Wuarin","year":"1994","unstructured":"Wuarin, J. & Schibler, U. Physical isolation of nascent RNA chains transcribed by RNA polymerase II: evidence for cotranscriptional splicing. Mol. Cell. Biol. 14, 7219\u20137225 (1994).","journal-title":"Mol. Cell. Biol."},{"key":"7969_CR52","doi-asserted-by":"publisher","first-page":"e67","DOI":"10.1093\/nar\/gkm193","volume":"35","author":"JR Henriksen","year":"2007","unstructured":"Henriksen, J. R. et al. Comparison of RNAi efficiency mediated by tetracycline-responsive H1 and U6 promoter variants in mammalian cell lines. Nucleic Acids Res. 35, e67 (2007).","journal-title":"Nucleic Acids Res."},{"key":"7969_CR53","unstructured":"Blue, S., Nostrand E. V. & Yeo, G. Biotin-labelling of immunoprecipitated RNA (v1pre). protocols.io protocols.io\/view\/biotin-labelling-of-immunoprecipitated-rna-v1pre-cbehsjb6 (2022)."},{"key":"7969_CR54","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114\u20132120 (2014).","journal-title":"Bioinformatics"},{"key":"7969_CR55","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"7969_CR56","doi-asserted-by":"crossref","unstructured":"Zhang, Y. et al. Model-based analysis of ChIP\u2013seq (MACS). Genome Biol. 9, R137 (2008).","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"7969_CR57","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1093\/bioinformatics\/btt650","volume":"30","author":"M Lienhard","year":"2014","unstructured":"Lienhard, M., Grimm, C., Morkel, M., Herwig, R. & Chavez, L. MEDIPS: genome-wide differential coverage analysis of sequencing data derived from DNA enrichment experiments. Bioinformatics 30, 284\u2013286 (2014).","journal-title":"Bioinformatics"},{"key":"7969_CR58","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","volume":"37","author":"D Kim","year":"2019","unstructured":"Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37, 907\u2013915 (2019).","journal-title":"Nat. Biotechnol."},{"key":"7969_CR59","doi-asserted-by":"publisher","first-page":"D766","DOI":"10.1093\/nar\/gky955","volume":"47","author":"A Frankish","year":"2019","unstructured":"Frankish, A. et al. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res. 47, D766\u2013D773 (2019).","journal-title":"Nucleic Acids Res."},{"key":"7969_CR60","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders, S., Pyl, P. T. & Huber, W. HTSeq-a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166\u2013169 (2015).","journal-title":"Bioinformatics"},{"key":"7969_CR61","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"7969_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25","volume":"10","author":"B Langmead","year":"2009","unstructured":"Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).","journal-title":"Genome Biol."},{"key":"7969_CR63","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008","volume":"10","author":"P Danecek","year":"2021","unstructured":"Danecek, P. et al. Twelve years of SAMtools and BCFtools. Gigascience 10, giab008 (2021).","journal-title":"Gigascience"},{"key":"7969_CR64","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923\u2013930 (2014).","journal-title":"Bioinformatics"},{"key":"7969_CR65","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"7969_CR66","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1101\/gr.275193.120","volume":"31","author":"Y Zhang","year":"2021","unstructured":"Zhang, Y., Park, C., Bennett, C., Thornton, M. & Kim, D. Rapid and accurate alignment of nucleotide conversion sequencing reads with HISAT-3N. Genome Res. 31, 1290\u20131295 (2021).","journal-title":"Genome Res."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-024-07969-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-024-07969-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-024-07969-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T06:05:16Z","timestamp":1731650716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-024-07969-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,2]]},"references-count":66,"journal-issue":{"issue":"8035","published-print":{"date-parts":[[2024,10,24]]}},"alternative-id":["7969"],"URL":"https:\/\/doi.org\/10.1038\/s41586-024-07969-x","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,2]]},"assertion":[{"value":"25 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This article was originally published under a CC BY-NC-ND 4.0 license, but has now been made available under a Creative Commons Attribution 4.0 International License.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors have filed a provision patent application of targets reported in this paper through the University of Chicago. C.H. is a scientific founder, a member of the scientific advisory board and equity holder of Aferna Bio and Ellis Bio, a scientific cofounder and equity holder of Accent Therapeutics, and a member of the scientific advisory board of Rona Therapeutics and Element Biosciences. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}