{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:10:44Z","timestamp":1762297844745,"version":"build-2065373602"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770787","82273036"],"award-info":[{"award-number":["81770787","82273036"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Mol Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ten eleven translocation 1 (TET1) is a 5-methylcytosine dioxygenase, and its altered DNA demethylation has been implicated in human diseases. However, its role in regulating thyroid function remains totally unknown. Here we first generated thyroid-specific\n                    <jats:italic>Tet1<\/jats:italic>\n                    knockout combined with thyroid-specific\n                    <jats:italic>Braf<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V600E<\/jats:italic>\n                    <\/jats:sup>\n                    transgenic mouse model (\n                    <jats:italic>Thy-Braf<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V600E<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>; Tet1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) and their control mice (\n                    <jats:italic>Thy-Braf<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V600E<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>; Tet1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    ). The latter developed severe hypothyroidism and lost reproductive ability owing to structural damages of thyroid gland, while thyroid-specific\n                    <jats:italic>Tet1<\/jats:italic>\n                    knockout effectively restored thyroid structure and function of\n                    <jats:italic>Thy-Braf<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V600E<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>; Tet1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    mice and their reproductive ability. In addition, we also established thyroid-specific\n                    <jats:italic>Tet1<\/jats:italic>\n                    knockout mouse model (\n                    <jats:italic>Thy-Tet1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) and demonstrated that these mice could develop hyperthyroidism with systemic hypermetabolic symptoms such as weight loss, increased heart rate and elevated systolic blood pressure, further supporting the inhibitory effect of TET1 on thyroid function. Transcriptomic sequencing revealed that key genes related to metabolism and synthesis of thyroid hormones such as\n                    <jats:italic>PAX8<\/jats:italic>\n                    ,\n                    <jats:italic>SLC5A5<\/jats:italic>\n                    and\n                    <jats:italic>TPO<\/jats:italic>\n                    were significantly upregulated in\n                    <jats:italic>Thy-Tet1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Mechanistically, TET1 recruits HDAC1 to reduce the levels of H3K27Ac and H3K9Ac in the\n                    <jats:italic>PAX8<\/jats:italic>\n                    promoter, thereby inhibiting the expression of itself and its downstream targets NIS and TPO. Further studies showed that elevated miR-29c-3p in serum exosomes enhanced thyroid function by targeting TET1, which may be one of the causes of hyperthyroidism. Thus, this study uncovers a new mechanism by which TET1 suppresses thyroid function, providing a new perspective to explore the pathogenesis of hyperthyroidism.\n                  <\/jats:p>","DOI":"10.1038\/s12276-025-01566-2","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T02:27:20Z","timestamp":1761704840000},"page":"2376-2392","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TET1 loss propels the development of hyperthyroidism by remodeling histone modifications of PAX8 promoter"],"prefix":"10.1038","volume":"57","author":[{"given":"Hui","family":"Dang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengjun","family":"Sui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8572-7142","authenticated-orcid":false,"given":"Yubo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Qiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Sui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiju","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7010-7944","authenticated-orcid":false,"given":"Peng","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"1566_CR1","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/S0140-6736(16)00278-6","volume":"388","author":"S De Leo","year":"2016","unstructured":"De Leo, S., Lee, S. Y. & Braverman, L. E. Hyperthyroidism. Lancet 388, 906\u2013918 (2016).","journal-title":"Lancet"},{"key":"1566_CR2","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1210\/jc.2013-2409","volume":"99","author":"A Garmendia Madariaga","year":"2014","unstructured":"Garmendia Madariaga, A., Santos Palacios, S., Guill\u00e9n-Grima, F. & Galofr\u00e9, J. C. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J. Clin. Endocrinol. Metab. 99, 923\u2013931 (2014).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"1566_CR3","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1210\/jcem.87.2.8182","volume":"87","author":"JG Hollowell","year":"2002","unstructured":"Hollowell, J. G. et al. Serum TSH, T (4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 87, 489\u2013499 (2002).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"1566_CR4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.beem.2009.08.013","volume":"24","author":"P Laurberg","year":"2010","unstructured":"Laurberg, P. et al. Iodine intake as a determinant of thyroid disorders in populations. Best Pract. Res. Clin. Endocrinol. Metab. 24, 13\u201327 (2010).","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"1566_CR5","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/S2213-8587(14)70225-6","volume":"3","author":"MB Zimmermann","year":"2015","unstructured":"Zimmermann, M. B. & Boelaert, K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. 3, 286\u2013295 (2015).","journal-title":"Lancet Diabetes Endocrinol."},{"key":"1566_CR6","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41580-019-0159-6","volume":"20","author":"MVC Greenberg","year":"2019","unstructured":"Greenberg, M. V. C. & Bourc\u2019his, D. The diverse roles of DNA methylation in mammalian development and disease. Nat. Rev. Mol. Cell Biol. 20, 590\u2013607 (2019).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1566_CR7","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrg.2017.33","volume":"18","author":"X Wu","year":"2017","unstructured":"Wu, X. & Zhang, Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat. Rev. Genet. 18, 517\u2013534 (2017).","journal-title":"Nat. Rev. Genet."},{"key":"1566_CR8","volume":"15","author":"Z Chen","year":"2023","unstructured":"Chen, Z. et al. Phosphorylation stabilized TET1 acts as an oncoprotein and therapeutic target in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 15, eabq8513 (2023).","journal-title":"Sci. Transl. Med."},{"key":"1566_CR9","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.neuron.2013.08.003","volume":"79","author":"A Rudenko","year":"2013","unstructured":"Rudenko, A. et al. Tet1 is critical for neuronal activity-regulated gene expression and memory extinction. Neuron 79, 1109\u20131122 (2013).","journal-title":"Neuron"},{"key":"1566_CR10","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/ni.3148","volume":"16","author":"L Cimmino","year":"2015","unstructured":"Cimmino, L. et al. TET1 is a tumor suppressor of hematopoietic malignancy. Nat. Immunol. 16, 653\u2013662 (2015).","journal-title":"Nat. Immunol."},{"key":"1566_CR11","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1093\/nar\/gkac089","volume":"50","author":"S Chrysanthou","year":"2022","unstructured":"Chrysanthou, S. et al. The DNA dioxygenase Tet1 regulates H3K27 modification and embryonic stem cell biology independent of its catalytic activity. Nucleic Acids Res. 50, 3169\u20133189 (2022).","journal-title":"Nucleic Acids Res"},{"key":"1566_CR12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41580-021-00441-y","volume":"23","author":"M Shvedunova","year":"2022","unstructured":"Shvedunova, M. & Akhtar, A. Modulation of cellular processes by histone and non-histone protein acetylation. Nat. Rev. Mol. Cell Biol. 23, 329\u2013349 (2022).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1566_CR13","doi-asserted-by":"crossref","first-page":"113746","DOI":"10.1016\/j.celrep.2024.113746","volume":"43","author":"W Shi","year":"2024","unstructured":"Shi, W., Cassmann, T. J., Bhagwate, A. V., Hitosugi, T. & Ip, W. K. E. Lactic acid induces transcriptional repression of macrophage inflammatory response via histone acetylation. Cell Rep. 43, 113746 (2024).","journal-title":"Cell Rep."},{"key":"1566_CR14","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s13238-021-00846-7","volume":"13","author":"L Sun","year":"2022","unstructured":"Sun, L., Zhang, H. & Gao, P. Metabolic reprogramming and epigenetic modifications on the path to cancer. Protein Cell 13, 877\u2013919 (2022).","journal-title":"Protein Cell"},{"key":"1566_CR15","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1073\/pnas.1015557108","volume":"108","author":"AT Franco","year":"2011","unstructured":"Franco, A. T. et al. Thyrotrophin receptor signaling dependence of Braf-induced thyroid tumor initiation in mice. Proc. Natl Acad. Sci. USA 108, 1615\u20131620 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1566_CR16","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1186\/s13046-021-02195-z","volume":"40","author":"S Ma","year":"2021","unstructured":"Ma, S. et al. ZIP10 is a negative determinant for anti-tumor effect of mannose in thyroid cancer by activating phosphate mannose isomerase. J. Exp. Clin. Cancer Res. 40, 387 (2021).","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"1566_CR17","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1038\/s41388-023-02659-w","volume":"42","author":"Q Yang","year":"2023","unstructured":"Yang, Q. et al. Hypoxia switches TET1 from being tumor-suppressive to oncogenic. Oncogene 42, 1634\u20131648 (2023).","journal-title":"Oncogene"},{"key":"1566_CR18","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s12020-022-03202-9","volume":"78","author":"J Ma","year":"2022","unstructured":"Ma, J. et al. Sorafenib decreases glycemia by impairing hepatic glucose metabolism. Endocrine 78, 446\u2013457 (2022).","journal-title":"Endocrine"},{"key":"1566_CR19","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1089\/thy.2018.0183","volume":"28","author":"Y Li","year":"2018","unstructured":"Li, Y. et al. c-Myc is a major determinant for antitumor activity of aurora a kinase inhibitor MLN8237 in thyroid cancer. Thyroid 28, 1642\u20131654 (2018).","journal-title":"Thyroid"},{"key":"1566_CR20","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/gene.20043","volume":"39","author":"T Kusakabe","year":"2004","unstructured":"Kusakabe, T., Kawaguchi, A., Kawaguchi, R., Feigenbaum, L. & Kimura, S. Thyrocyte-specific expression of Cre recombinase in transgenic mice. Genesis 39, 212\u2013216 (2004).","journal-title":"Genesis"},{"key":"1566_CR21","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1210\/er.2009-0041","volume":"31","author":"GE Krassas","year":"2010","unstructured":"Krassas, G. E., Poppe, K. & Glinoer, D. Thyroid function and human reproductive health. Endocr. Rev. 31, 702\u2013755 (2010).","journal-title":"Endocr. Rev."},{"key":"1566_CR22","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/cvr\/cvz132","volume":"115","author":"G Caligiuri","year":"2019","unstructured":"Caligiuri, G. Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology. Cardiovasc. Res. 115, 1425\u20131434 (2019).","journal-title":"Cardiovasc. Res."},{"key":"1566_CR23","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1146\/annurev.me.37.020186.002033","volume":"37","author":"GF Bottazzo","year":"1986","unstructured":"Bottazzo, G. F. & Doniach, D. Autoimmune thyroid disease. Annu. Rev. Med. 37, 353\u2013359 (1986).","journal-title":"Annu. Rev. Med."},{"key":"1566_CR24","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1586\/1744666X.4.2.221","volume":"4","author":"N Takasu","year":"2008","unstructured":"Takasu, N. & Yoshimura Noh, J. Hashimoto\u2019s thyroiditis: TGAb, TPOAb, TRAb and recovery from hypothyroidism. Expert Rev. Clin. Immunol. 4, 221\u2013237 (2008).","journal-title":"Expert Rev. Clin. Immunol."},{"key":"1566_CR25","doi-asserted-by":"crossref","first-page":"474","DOI":"10.3389\/fendo.2018.00474","volume":"9","author":"AG Cicatiello","year":"2018","unstructured":"Cicatiello, A. G., Di Girolamo, D. & Dentice, M. Metabolic effects of the intracellular regulation of thyroid hormone: old players, new concepts. Front. Endocrinol. 9, 474 (2018).","journal-title":"Front. Endocrinol."},{"key":"1566_CR26","doi-asserted-by":"crossref","first-page":"13144","DOI":"10.1073\/pnas.240336397","volume":"97","author":"M Pasca di Magliano","year":"2000","unstructured":"Pasca di Magliano, M., Di Lauro, R. & Zannini, M. Pax8 has a key role in thyroid cell differentiation. Proc. Natl Acad. Sci. USA 97, 13144\u201313149 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1566_CR27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nrendo.2014.186","volume":"11","author":"LP Fern\u00e1ndez","year":"2015","unstructured":"Fern\u00e1ndez, L. P., L\u00f3pez-M\u00e1rquez, A. & Santisteban, P. Thyroid transcription factors in development, differentiation and disease. Nat. Rev. Endocrinol. 11, 29\u201342 (2015).","journal-title":"Nat. Rev. Endocrinol."},{"key":"1566_CR28","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1158\/0008-5472.CAN-14-3547","volume":"75","author":"G Riesco-Eizaguirre","year":"2015","unstructured":"Riesco-Eizaguirre, G., Wert-Lamas, L., Perales-Pat\u00f3n, J., Sastre-Perona, A., Fern\u00e1ndez, L. P. & Santisteban, P. The miR-146b-3p\/PAX8\/NIS regulatory circuit modulates the differentiation phenotype and function of thyroid cells during carcinogenesis. Cancer Res. 75, 4119\u20134130 (2015).","journal-title":"Cancer Res"},{"key":"1566_CR29","doi-asserted-by":"crossref","unstructured":"Wen G, Eder K, Ringseis R. Resveratrol Alleviates the Inhibitory Effect of Tunicamycin-Induced Endoplasmic Reticulum Stress on Expression of Genes Involved in Thyroid Hormone Synthesis in FRTL-5 Thyrocytes. Int J Mol. Sci. 22, 4373 (2021).","DOI":"10.3390\/ijms22094373"},{"key":"1566_CR30","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.cell.2011.03.022","volume":"145","author":"JU Guo","year":"2011","unstructured":"Guo, J. U., Su, Y., Zhong, C., Ming, G. L. & Song, H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145, 423\u2013434 (2011).","journal-title":"Cell"},{"key":"1566_CR31","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-18054-y","volume":"11","author":"S Damal Villivalam","year":"2020","unstructured":"Damal Villivalam, S. et al. TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis. Nat. Commun. 11, 4313 (2020).","journal-title":"Nat. Commun."},{"key":"1566_CR32","volume":"6","author":"L Zheng","year":"2016","unstructured":"Zheng, L. et al. The modification of Tet1 in male germline stem cells and interact with PCNA, HDAC1 to promote their self-renewal and proliferation. Sci. Rep. 6, 37414 (2016).","journal-title":"Sci. Rep."},{"key":"1566_CR33","doi-asserted-by":"crossref","first-page":"32775","DOI":"10.1074\/jbc.M111.248278","volume":"286","author":"S Chen","year":"2011","unstructured":"Chen, S. et al. Histone deacetylase (HDAC) activity is critical for embryonic kidney gene expression, growth, and differentiation. J. Biol. Chem. 286, 32775\u201332789 (2011).","journal-title":"J. Biol. Chem."},{"key":"1566_CR34","doi-asserted-by":"crossref","unstructured":"Shi, K. et al. PAX8 regulon in human ovarian cancer links lineage dependency with epigenetic vulnerability to HDAC inhibitors. eLife 8, e44306 (2019).","DOI":"10.7554\/eLife.44306"},{"key":"1566_CR35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1530\/ERC-13-0399","volume":"21","author":"Z Zhang","year":"2014","unstructured":"Zhang, Z., Liu, D., Murugan, A. K., Liu, Z. & Xing, M. Histone deacetylation of NIS promoter underlies BRAF V600E-promoted NIS silencing in thyroid cancer. Endocr. Relat. Cancer 21, 161\u2013173 (2014).","journal-title":"Endocr. Relat. Cancer"},{"key":"1566_CR36","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1089\/thy.2016.0062","volume":"26","author":"I Hiratsuka","year":"2016","unstructured":"Hiratsuka, I., Yamada, H., Munetsuna, E., Hashimoto, S. & Itoh, M. Circulating MicroRNAs in Graves\u2019 disease in relation to clinical activity. Thyroid 26, 1431\u20131440 (2016).","journal-title":"Thyroid"},{"key":"1566_CR37","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ceb.2004.06.003","volume":"16","author":"B F\u00e9vrier","year":"2004","unstructured":"F\u00e9vrier, B. & Raposo, G. Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr. Opin. Cell Biol. 16, 415\u2013421 (2004).","journal-title":"Curr. Opin. Cell Biol."},{"key":"1566_CR38","doi-asserted-by":"crossref","first-page":"e21916","DOI":"10.1096\/fj.202100294RR","volume":"35","author":"B Li","year":"2021","unstructured":"Li, B., Cao, Y., Sun, M. & Feng, H. Expression, regulation, and function of exosome-derived miRNAs in cancer progression and therapy. FASEB J. 35, e21916 (2021).","journal-title":"FASEB J."},{"key":"1566_CR39","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1126\/science.7209519","volume":"212","author":"WJ Beamer","year":"1981","unstructured":"Beamer, W. J., Eicher, E. M., Maltais, L. J. & Southard, J. L. Inherited primary hypothyroidism in mice. Science 212, 61\u201363 (1981).","journal-title":"Science"},{"key":"1566_CR40","doi-asserted-by":"crossref","first-page":"205873841877524","DOI":"10.1177\/2058738418775241","volume":"32","author":"S La Vignera","year":"2018","unstructured":"La Vignera, S. & Vita, R. Thyroid dysfunction and semen quality. Int. J. Immunopathol. Pharmacol. 32, 2058738418775241 (2018).","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"1566_CR41","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/s41588-022-01119-7","volume":"54","author":"BK Wu","year":"2022","unstructured":"Wu, B. K., Mei, S. C., Chen, E. H., Zheng, Y. & Pan, D. YAP induces an oncogenic transcriptional program through TET1-mediated epigenetic remodeling in liver growth and tumorigenesis. Nat. Genet. 54, 1202\u20131213 (2022).","journal-title":"Nat. Genet."},{"key":"1566_CR42","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.cmet.2020.10.021","volume":"33","author":"H Lv","year":"2021","unstructured":"Lv, H. et al. NAD(+) Metabolism maintains inducible PD-L1 expression to drive tumor immune evasion. Cell Metab. 33, 110\u2013127.e115 (2021).","journal-title":"Cell Metab."},{"key":"1566_CR43","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s13148-021-01201-7","volume":"13","author":"U Schagdarsurengin","year":"2021","unstructured":"Schagdarsurengin, U. et al. Tracing TET1 expression in prostate cancer: discovery of malignant cells with a distinct oncogenic signature. Clin. Epigenet. 13, 211 (2021).","journal-title":"Clin. Epigenet."},{"key":"1566_CR44","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1016\/j.ygeno.2021.04.033","volume":"113","author":"M Mao","year":"2021","unstructured":"Mao, M. et al. OCT3\/4 enhances tumor immune response by upregulating the TET1-dependent NRF2\/MDM2 axis in bladder cancer. Genomics 113, 2122\u20132133 (2021).","journal-title":"Genomics"},{"key":"1566_CR45","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbalip.2021.158919","volume":"1866","author":"H Qian","year":"2021","unstructured":"Qian, H. et al. TET1 promotes RXR\u03b1 expression and adipogenesis through DNA demethylation. BBA Mol. Cell Biol. Lipids 1866, 158919 (2021).","journal-title":"BBA Mol. Cell Biol. Lipids"},{"key":"1566_CR46","doi-asserted-by":"crossref","unstructured":"Zhang, C. et al. The hepatic AMPK\u2013TET1\u2013SIRT1 axis regulates glucose homeostasis. eLife 10, e70672 (2021).","DOI":"10.7554\/eLife.70672"},{"key":"1566_CR47","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/j.2040-4603.2016.tb00708.x","volume":"6","author":"TM Ortiga-Carvalho","year":"2016","unstructured":"Ortiga-Carvalho, T. M., Chiamolera, M. I., Pazos-Moura, C. C. & Wondisford, F. E. Hypothalamus\u2013pituitary\u2013thyroid axis. Compr. Physiol. 6, 1387\u20131428 (2016).","journal-title":"Compr. Physiol."},{"key":"1566_CR48","doi-asserted-by":"crossref","first-page":"4896","DOI":"10.1038\/sj.onc.1203852","volume":"19","author":"JA Du Villard","year":"2000","unstructured":"Du Villard, J. A. et al. Role of the cAMP and MAPK pathways in the transformation of mouse 3T3 fibroblasts by a TSHR gene constitutively activated by point mutation. Oncogene 19, 4896\u20134905 (2000).","journal-title":"Oncogene"},{"key":"1566_CR49","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1210\/er.2015-1106","volume":"37","author":"JH Bassett","year":"2016","unstructured":"Bassett, J. H. & Williams, G. R. Role of thyroid hormones in skeletal development and bone maintenance. Endocr. Rev. 37, 135\u2013187 (2016).","journal-title":"Endocr. Rev."},{"key":"1566_CR50","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nature11925","volume":"495","author":"Y Costa","year":"2013","unstructured":"Costa, Y. et al. NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature 495, 370\u2013374 (2013).","journal-title":"Nature"},{"key":"1566_CR51","doi-asserted-by":"crossref","first-page":"9369","DOI":"10.1080\/21655979.2022.2054762","volume":"13","author":"L Wang","year":"2022","unstructured":"Wang, L. et al. Dexmedetomidine prevents cardiomyocytes from hypoxia\/reoxygenation injury via modulating tetmethylcytosine dioxygenase 1-mediated DNA demethylation of Sirtuin1. Bioengineered 13, 9369\u20139386 (2022).","journal-title":"Bioengineered"},{"key":"1566_CR52","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13287-022-02797-0","volume":"13","author":"Y Yi","year":"2022","unstructured":"Yi, Y. et al. Ascorbic acid 2-glucoside preconditioning enhances the ability of bone marrow mesenchymal stem cells in promoting wound healing. Stem Cell Res. Ther. 13, 119 (2022).","journal-title":"Stem Cell Res. Ther."},{"key":"1566_CR53","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature10066","volume":"473","author":"K Williams","year":"2011","unstructured":"Williams, K. et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473, 343\u2013348 (2011).","journal-title":"Nature"},{"key":"1566_CR54","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1101\/gad.2036011","volume":"25","author":"H Wu","year":"2011","unstructured":"Wu, H. et al. Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev. 25, 679\u2013684 (2011).","journal-title":"Genes Dev."},{"key":"1566_CR55","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/nar\/gkw919","volume":"45","author":"J Zhong","year":"2017","unstructured":"Zhong, J. et al. TET1 modulates H4K16 acetylation by controlling auto-acetylation of hMOF to affect gene regulation and DNA repair function. Nucleic Acids Res. 45, 672\u2013684 (2017).","journal-title":"Nucleic Acids Res"},{"key":"1566_CR56","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3389\/fgene.2020.00069","volume":"11","author":"Z Zhu","year":"2020","unstructured":"Zhu, Z., Jin, Z., Zhang, H., Zhang, M. & Sun, D. Integrative clustering reveals a novel subtype of soft tissue sarcoma with poor prognosis. Front. Genet. 11, 69 (2020).","journal-title":"Front. Genet."},{"key":"1566_CR57","doi-asserted-by":"crossref","first-page":"14647","DOI":"10.3390\/ijms140714647","volume":"14","author":"S Morita","year":"2013","unstructured":"Morita, S., Horii, T., Kimura, M., Ochiya, T., Tajima, S. & Hatada, I. miR-29 represses the activities of DNA methyltransferases and DNA demethylases. Int. J. Mol. Sci. 14, 14647\u201314658 (2013).","journal-title":"Int. J. Mol. Sci."},{"key":"1566_CR58","first-page":"1064","volume":"33","author":"F Sui","year":"2023","unstructured":"Sui, F. et al. A feedback loop involving exosomal miR-146a and NG2 to propel the development and progression of hypothyroidism. Thyroid 33, 1064\u20131077 (2023).","journal-title":"Thyroid"}],"container-title":["Experimental &amp; Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s12276-025-01566-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s12276-025-01566-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s12276-025-01566-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:04:33Z","timestamp":1762297473000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s12276-025-01566-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":58,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["1566"],"URL":"https:\/\/doi.org\/10.1038\/s12276-025-01566-2","relation":{},"ISSN":["2092-6413"],"issn-type":[{"type":"electronic","value":"2092-6413"}],"subject":[],"published":{"date-parts":[[2025,10,29]]},"assertion":[{"value":"24 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors consent to publish the paper.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}