{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T04:38:47Z","timestamp":1793248727543,"version":"4.5.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"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":["82170621"],"award-info":[{"award-number":["82170621"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mineral dust-induced gene (MDIG) comprises a conserved JmjC domain and has the ability to demethylate histone H3 lysine 9 trimethylation (H3K9me3). Previous studies have indicated the significance of MDIG in promoting cell proliferation by modulating cell-cycle transition. However, its involvement in liver regeneration has not been extensively investigated. In this study, we generated mice with liver-specific knockout of MDIG and applied partial hepatectomy or carbon tetrachloride mouse models to investigate the biological contribution of MDIG in liver regeneration. The MDIG levels showed initial upregulation followed by downregulation as the recovery progressed. Genetic MDIG deficiency resulted in dramatically impaired liver regeneration and delayed cell cycle progression. However, the MDIG-deleted liver was eventually restored over a long latency. RNA-seq analysis revealed Myc as a crucial effector downstream of MDIG. However, ATAC-seq identified the reduced chromatin accessibility of OTX2 locus in MDIG-ablated regenerating liver, with unaltered chromatin accessibility of Myc locus. Mechanistically, MDIG altered chromatin accessibility to allow transcription by demethylating H3K9me3 at the OTX2 promoter region. As a consequence, the transcription factor OTX2 binding at the Myc promoter region was decreased in MDIG-deficient hepatocytes, which in turn repressed Myc expression. Reciprocally, Myc enhanced MDIG expression by regulating MDIG promoter activity, forming a positive feedback loop to sustain hepatocyte proliferation. Altogether, our results prove the essential role of MDIG in facilitating liver regeneration via regulating histone methylation to alter chromatin accessibility and provide valuable insights into the epi-transcriptomic regulation during liver regeneration.<\/jats:p>","DOI":"10.1038\/s41392-023-01575-5","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:01:55Z","timestamp":1694736115000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["MDIG-mediated H3K9me3 demethylation upregulates Myc by activating OTX2 and facilitates liver regeneration"],"prefix":"10.1038","volume":"8","author":[{"given":"Jinpeng","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwei","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6886-5698","authenticated-orcid":false,"given":"Haichuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guimin","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4308-7743","authenticated-orcid":false,"given":"Kefei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3347-9690","authenticated-orcid":false,"given":"Yong","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"1575_CR1","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41580-021-00373-7","volume":"22","author":"L Campana","year":"2021","unstructured":"Campana, L., Esser, H., Huch, M. & Forbes, S. Liver regeneration and inflammation: from fundamental science to clinical applications. Nat. Rev. Mol. Cell Biol. 22, 608\u2013624 (2021).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1575_CR2","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1126\/science.276.5309.60","volume":"276","author":"GK Michalopoulos","year":"1997","unstructured":"Michalopoulos, G. K. & DeFrances, M. C. Liver regeneration. Science. 276, 60\u201366 (1997).","journal-title":"Science."},{"key":"1575_CR3","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1096\/fasebj.10.4.8647340","volume":"10","author":"R Taub","year":"1996","unstructured":"Taub, R. Liver regeneration 4: transcriptional control of liver regeneration. FASEB J. 10, 413\u2013427 (1996).","journal-title":"FASEB J."},{"key":"1575_CR4","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/hep.23059","volume":"50","author":"U Apte","year":"2009","unstructured":"Apte, U. et al. Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase. Hepatology. 50, 844\u2013851 (2009).","journal-title":"Hepatology."},{"key":"1575_CR5","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nrgastro.2013.55","volume":"10","author":"C Lim","year":"2013","unstructured":"Lim, C. et al. Tumour progression and liver regeneration\u2013insights from animal models. Nat. Rev. Gastroenterol. Hepatol. 10, 452\u2013462 (2013).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"1575_CR6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41575-020-0342-4","volume":"18","author":"GK Michalopoulos","year":"2021","unstructured":"Michalopoulos, G. K. & Bhushan, B. Liver regeneration: biological and pathological mechanisms and implications. Nat. Rev. Gastroenterol. Hepatol. 18, 40\u201355 (2021).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"1575_CR7","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.cell.2013.02.014","volume":"152","author":"TI Lee","year":"2013","unstructured":"Lee, T. I. & Young, R. A. Transcriptional regulation and its misregulation in disease. Cell. 152, 1237\u20131251 (2013).","journal-title":"Cell."},{"key":"1575_CR8","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/nature18606","volume":"534","author":"J Wu","year":"2016","unstructured":"Wu, J. et al. The landscape of accessible chromatin in mammalian preimplantation embryos. Nature. 534, 652\u2013657 (2016).","journal-title":"Nature."},{"key":"1575_CR9","volume":"12","author":"C Zhang","year":"2021","unstructured":"Zhang, C., Macchi, F., Magnani, E. & Sadler, K. C. Chromatin states shaped by an epigenetic code confer regenerative potential to the mouse liver. Nat. Commun. 12, 4110 (2021).","journal-title":"Nat. Commun."},{"key":"1575_CR10","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nrg2072","volume":"8","author":"RK Slotkin","year":"2007","unstructured":"Slotkin, R. K. & Martienssen, R. Transposable elements and the epigenetic regulation of the genome. Nat. Rev. Genet. 8, 272\u2013285 (2007).","journal-title":"Nat. Rev. Genet."},{"key":"1575_CR11","doi-asserted-by":"crossref","unstructured":"Mill\u00e1n-Zambrano, G., Burton, A., Bannister, A. J. & Schneider, R. Histone post-translational modifications - cause and consequence of genome function. Nat. Rev. Genet. 23, 563\u2013580 (2022).","DOI":"10.1038\/s41576-022-00468-7"},{"key":"1575_CR12","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","volume":"128","author":"T Kouzarides","year":"2007","unstructured":"Kouzarides, T. Chromatin modifications and their function. Cell. 128, 693\u2013705 (2007).","journal-title":"Cell."},{"key":"1575_CR13","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/35065138","volume":"410","author":"AJ Bannister","year":"2001","unstructured":"Bannister, A. J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature. 410, 120\u2013124 (2001).","journal-title":"Nature."},{"key":"1575_CR14","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1016\/j.biochi.2012.08.011","volume":"94","author":"J Gupta","year":"2012","unstructured":"Gupta, J. et al. Histone H3 lysine 4 monomethylation (H3K4me1) and H3 lysine 9 monomethylation (H3K9me1): distribution and their association in regulating gene expression under hyperglycaemic\/hyperinsulinemic conditions in 3T3 cells. Biochimie. 94, 2656\u20132664 (2012).","journal-title":"Biochimie."},{"key":"1575_CR15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41392-018-0027-4","volume":"3","author":"C Thakur","year":"2018","unstructured":"Thakur, C. et al. Loss of mdig expression enhances DNA and histone methylation and metastasis of aggressive breast cancer. Signal Transduct Target Ther. 3, 25 (2018).","journal-title":"Signal Transduct Target Ther."},{"key":"1575_CR16","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1158\/0008-5472.CAN-19-3226","volume":"80","author":"L Zhang","year":"2020","unstructured":"Zhang, L. et al. ZNF143-mediated H3K9 trimethylation upregulates CDC6 by activating MDIG in hepatocellular carcinoma. Cancer Res. 80, 2599\u20132611 (2020).","journal-title":"Cancer Res."},{"key":"1575_CR17","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1158\/0008-5472.CAN-18-1310","volume":"79","author":"Y Xiang","year":"2019","unstructured":"Xiang, Y. et al. Histone demethylase KDM4B promotes DNA damage by activating long interspersed nuclear element-1. Cancer Res. 79, 86\u201398 (2019).","journal-title":"Cancer Res."},{"key":"1575_CR18","doi-asserted-by":"crossref","first-page":"4873","DOI":"10.1038\/sj.onc.1208668","volume":"24","author":"Y Zhang","year":"2005","unstructured":"Zhang, Y. et al. The human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer. Oncogene. 24, 4873\u20134882 (2005).","journal-title":"Oncogene."},{"key":"1575_CR19","doi-asserted-by":"crossref","first-page":"35450","DOI":"10.1074\/jbc.M204458200","volume":"277","author":"M Tsuneoka","year":"2002","unstructured":"Tsuneoka, M. et al. A novel myc target gene, mina53, that is involved in cell proliferation. J. Biol. Chem. 277, 35450\u201335459 (2002).","journal-title":"J. Biol. Chem."},{"key":"1575_CR20","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.4161\/cc.8.13.8927","volume":"8","author":"Y Lu","year":"2009","unstructured":"Lu, Y. et al. Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3. Cell Cycle. 8, 2101\u20132109 (2009).","journal-title":"Cell Cycle."},{"key":"1575_CR21","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/onc.2016.208","volume":"36","author":"MY Huang","year":"2017","unstructured":"Huang, M. Y., Xuan, F., Liu, W. & Cui, H. J. MINA controls proliferation and tumorigenesis of glioblastoma by epigenetically regulating cyclins and CDKs via H3K9me3 demethylation. Oncogene. 36, 387\u2013396 (2017).","journal-title":"Oncogene."},{"key":"1575_CR22","volume":"8","author":"Q Huo","year":"2017","unstructured":"Huo, Q. et al. Dysfunction of IKZF1\/MYC\/MDIG axis contributes to liver cancer progression through regulating H3K9me3\/p21 activity. Cell Death Dis. 8, e2766 (2017).","journal-title":"Cell Death Dis."},{"key":"1575_CR23","volume":"21","author":"HJ Lee","year":"2020","unstructured":"Lee, H. J. et al. Regenerating zebrafish fin epigenome is characterized by stable lineage-specific DNA methylation and dynamic chromatin accessibility. Genome Biol. 21, 52 (2020).","journal-title":"Genome Biol."},{"key":"1575_CR24","first-page":"647","volume":"7","author":"Y Lu","year":"2017","unstructured":"Lu, Y. et al. OTX2 expression contributes to proliferation and progression in Myc-amplified medulloblastoma. Am. J. Cancer Res. 7, 647\u2013656 (2017).","journal-title":"Am. J. Cancer Res."},{"key":"1575_CR25","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/cr.2017.117","volume":"27","author":"Z Lin","year":"2017","unstructured":"Lin, Z. et al. Mettl3-\/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis. Cell Res. 27, 1216\u20131230 (2017).","journal-title":"Cell Res."},{"key":"1575_CR26","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jhep.2015.08.036","volume":"64","author":"C Lu","year":"2016","unstructured":"Lu, C. et al. Loss of Gs\u03b1 impairs liver regeneration through a defect in the crosstalk between cAMP and growth factor signaling. J. Hepatol. 64, 342\u2013351 (2016).","journal-title":"J. Hepatol."},{"key":"1575_CR27","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1101\/gad.1455006","volume":"20","author":"Y Li","year":"2006","unstructured":"Li, Y. et al. A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity. Genes Dev. 20, 2566\u20132579 (2006).","journal-title":"Genes Dev."},{"key":"1575_CR28","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1002\/hep.26584","volume":"59","author":"W Hu","year":"2014","unstructured":"Hu, W. et al. Concurrent deletion of cyclin E1 and cyclin-dependent kinase 2 in hepatocytes inhibits DNA replication and liver regeneration in mice. Hepatology. 59, 651\u2013660 (2014).","journal-title":"Hepatology."},{"key":"1575_CR29","volume":"9","author":"XF Lu","year":"2018","unstructured":"Lu, X. F. et al. Histone deacetylase 3 promotes liver regeneration and liver cancer cells proliferation through signal transducer and activator of transcription 3 signaling pathway. Cell Death Dis. 9, 398 (2018).","journal-title":"Cell Death Dis."},{"key":"1575_CR30","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/laban1108-529","volume":"37","author":"S Boyce","year":"2008","unstructured":"Boyce, S. & Harrison, D. A detailed methodology of partial hepatectomy in the mouse. Lab Anim. 37, 529\u2013532 (2008).","journal-title":"Lab Anim."},{"key":"1575_CR31","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.jhep.2005.03.027","volume":"43","author":"S Haga","year":"2005","unstructured":"Haga, S. et al. Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice. J. Hepatol. 43, 799\u2013807 (2005).","journal-title":"J. Hepatol."},{"key":"1575_CR32","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/hep.28286","volume":"63","author":"M Pauta","year":"2016","unstructured":"Pauta, M. et al. Akt-mediated foxo1 inhibition is required for liver regeneration. Hepatology. 63, 1660\u20131674 (2016).","journal-title":"Hepatology."},{"key":"1575_CR33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0968-0004(97)01025-6","volume":"22","author":"C Grandori","year":"1997","unstructured":"Grandori, C. & Eisenman, R. N. Myc target genes. Trends Biochem. Sci. 22, 177\u2013181 (1997).","journal-title":"Trends Biochem. Sci."},{"key":"1575_CR34","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/nrc904","volume":"2","author":"S Pelengaris","year":"2002","unstructured":"Pelengaris, S., Khan, M. & Evan, G. c-MYC: more than just a matter of life and death. Nat. Rev. Cancer. 2, 764\u2013776 (2002).","journal-title":"Nat. Rev. Cancer."},{"key":"1575_CR35","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/nature13263","volume":"510","author":"R Chowdhury","year":"2014","unstructured":"Chowdhury, R. et al. Ribosomal oxygenases are structurally conserved from prokaryotes to humans. Nature 510, 422\u2013426 (2014).","journal-title":"Nature"},{"key":"1575_CR36","doi-asserted-by":"crossref","first-page":"E21","DOI":"10.1002\/ijc.26474","volume":"131","author":"J Bunt","year":"2012","unstructured":"Bunt, J. et al. OTX2 directly activates cell cycle genes and inhibits differentiation in medulloblastoma cells. Int. J. Cancer. 131, E21\u201332 (2012).","journal-title":"Int. J. Cancer."},{"key":"1575_CR37","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-17357-4","volume":"11","author":"J Zagozewski","year":"2020","unstructured":"Zagozewski, J. et al. An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate. Nat. Commun. 11, 3627 (2020).","journal-title":"Nat. Commun."},{"key":"1575_CR38","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.jcmgh.2021.04.001","volume":"12","author":"X Cao","year":"2021","unstructured":"Cao, X. et al. Mettl14-mediated m(6)A modification facilitates liver regeneration by maintaining endoplasmic reticulum homeostasis. Cell Mol. Gastroenterol. Hepatol. 12, 633\u2013651 (2021).","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"1575_CR39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.devcel.2019.05.034","volume":"50","author":"S Wang","year":"2019","unstructured":"Wang, S. et al. Epigenetic compensation promotes liver regeneration. Dev. Cell 50, 43\u201356.e46 (2019).","journal-title":"Dev. Cell"},{"key":"1575_CR40","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","volume":"2","author":"E Cerami","year":"2012","unstructured":"Cerami, E. et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401\u2013404 (2012).","journal-title":"Cancer Discov."},{"key":"1575_CR41","first-page":"pl1","volume":"6","author":"J Gao","year":"2013","unstructured":"Gao, J. et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 6, pl1 (2013).","journal-title":"Sci Signal."},{"key":"1575_CR42","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.tig.2020.05.002","volume":"36","author":"F Macchi","year":"2020","unstructured":"Macchi, F. & Sadler, K. C. Unraveling the epigenetic basis of liver development, regeneration and disease. Trends Genet. 36, 587\u2013597 (2020).","journal-title":"Trends Genet."},{"key":"1575_CR43","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev.biochem.75.103004.142422","volume":"75","author":"A Shilatifard","year":"2006","unstructured":"Shilatifard, A. Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu. Rev. Biochem. 75, 243\u2013269 (2006).","journal-title":"Annu. Rev. Biochem."},{"key":"1575_CR44","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/cr.2010.84","volume":"20","author":"H Lin","year":"2010","unstructured":"Lin, H. et al. Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans. Cell Res. 20, 899\u2013907 (2010).","journal-title":"Cell Res."},{"key":"1575_CR45","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jcmgh.2019.09.006","volume":"9","author":"AW Wang","year":"2020","unstructured":"Wang, A. W. et al. The dynamic chromatin architecture of the regenerating liver. Cell Mol Gastroenterol. Hepatol. 9, 121\u2013143 (2020).","journal-title":"Cell Mol Gastroenterol. Hepatol."},{"key":"1575_CR46","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.stem.2019.06.008","volume":"25","author":"W Li","year":"2019","unstructured":"Li, W. et al. A homeostatic Arid1a-dependent permissive chromatin state licenses hepatocyte responsiveness to liver-injury-associated YAP signaling. Cell Stem Cell 25, 54\u201368.e55 (2019).","journal-title":"Cell Stem Cell"},{"key":"1575_CR47","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm4043","volume":"16","author":"J Du","year":"2015","unstructured":"Du, J., Johnson, L. M., Jacobsen, S. E. & Patel, D. J. DNA methylation pathways and their crosstalk with histone methylation. Nat. Rev. Mol. Cell Biol. 16, 519\u2013532 (2015).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1575_CR48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gde.2019.04.013","volume":"55","author":"D Nicetto","year":"2019","unstructured":"Nicetto, D. & Zaret, K. S. Role of H3K9me3 heterochromatin in cell identity establishment and maintenance. Curr. Opin. Genet. Dev. 55, 1\u201310 (2019).","journal-title":"Curr. Opin. Genet. Dev."},{"key":"1575_CR49","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.cell.2012.08.026","volume":"151","author":"CY Lin","year":"2012","unstructured":"Lin, C. Y. et al. Transcriptional amplification in tumor cells with elevated c-Myc. Cell. 151, 56\u201367 (2012).","journal-title":"Cell."},{"key":"1575_CR50","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/nature13537","volume":"511","author":"A Sab\u00f2","year":"2014","unstructured":"Sab\u00f2, A. et al. Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis. Nature 511, 488\u2013492 (2014).","journal-title":"Nature"},{"key":"1575_CR51","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-15552-x","volume":"11","author":"MJ Bywater","year":"2020","unstructured":"Bywater, M. J. et al. Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity. Nat. Commun. 11, 1827 (2020).","journal-title":"Nat. Commun."},{"key":"1575_CR52","volume":"21","author":"J Du","year":"2022","unstructured":"Du, J. et al. CircNFIB inhibits tumor growth and metastasis through suppressing MEK1\/ERK signaling in intrahepatic cholangiocarcinoma. Mol. Cancer 21, 18 (2022).","journal-title":"Mol. Cancer"},{"key":"1575_CR53","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jhep.2021.08.021","volume":"76","author":"H Wang","year":"2022","unstructured":"Wang, H. et al. TAZ is indispensable for c-MYC-induced hepatocarcinogenesis. J. Hepatol. 76, 123\u2013134 (2022).","journal-title":"J. Hepatol."}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-023-01575-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-023-01575-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-023-01575-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T17:03:00Z","timestamp":1700240580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-023-01575-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,15]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1575"],"URL":"https:\/\/doi.org\/10.1038\/s41392-023-01575-5","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,15]]},"assertion":[{"value":"24 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2023","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"}}],"article-number":"351"}}