{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:34:26Z","timestamp":1777440866258,"version":"3.51.4"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Autophagy is an intracellular self-cannibalization process delivering cytoplasmic components to lysosomes for digestion. Autophagy has been reported to be involved in pulpitis, but the regulation of autophagy during pulpitis progression is largely unknown. To figure out the epigenetic regulation of autophagy during pulpitis, we screened several groups of histone methyltransferases and demethylases in response to TNF\u03b1 treatment. It was found JMJD3, a histone demethylase reducing di- and tri-methylation of H3K27, regulated the expression of several key autophagy genes via demethylation of H3K27me3 at the gene promoters. Our study highlighted the epigenetic regulation of autophagy genes during pulpitis, which will potentially provide a novel therapeutic strategy.<\/jats:p>","DOI":"10.3389\/fcell.2021.654958","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T08:09:31Z","timestamp":1628496571000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Epigenetic Control of Autophagy Related Genes Transcription in Pulpitis via JMJD3"],"prefix":"10.3389","volume":"9","author":[{"given":"Bei","family":"Yin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingge","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenghao","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenglin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanyuan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/978-1-4939-7352-1_18","article-title":"Autophagy monitoring assay II: imaging autophagy induction in LLC-PK1 cells using GFP-LC3 protein fusion construct.","volume":"1682","author":"Adiseshaiah","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6701","DOI":"10.1038\/onc.2017.267","article-title":"Lysine-specific demethylase LSD1 regulates autophagy in neuroblastoma through SESN2-dependent pathway.","volume":"36","author":"Ambrosio","year":"2017","journal-title":"Oncogene"},{"key":"B3","first-page":"1720","article-title":"Distribution of H3K27me3, H3K9me3, and H3K4me3 along autophagy-related genes highly expressed in starved zebrafish myotubes.","volume":"6","author":"Biga","year":"2017","journal-title":"Biol. Open"},{"key":"B4","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1083\/jcb.201706157","article-title":"Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins.","volume":"217","author":"Cadwell","year":"2018","journal-title":"J. Cell. Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.intimp.2016.02.023","article-title":"Emodin attenuates TNF-\u03b1-induced apoptosis and autophagy in mouse C2C12 myoblasts though the phosphorylation of Akt.","volume":"34","author":"Chen","year":"2016","journal-title":"Int. immunopharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1101\/gad.276428.115","article-title":"Distinct roles of autophagy-dependent and-independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model.","volume":"30","author":"Chen","year":"2016","journal-title":"Gene. Dev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1177\/0022034510393347","article-title":"Autophagic activity and aging in human odontoblasts.","volume":"90","author":"Couve","year":"2011","journal-title":"J. Dent. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1177\/0022034512449347","article-title":"Mitochondrial autophagy and lipofuscin accumulation in aging odontoblasts.","volume":"91","author":"Couve","year":"2012","journal-title":"J. Dental. Res."},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-06914-5","article-title":"RNA sequencing reveals resistance of TLR4 ligand-activated microglial cells to inflammation mediated by the selective jumonji H3K27 demethylase inhibitor.","volume":"7","author":"Das","year":"2017","journal-title":"Sci. Rep."},{"key":"B10","doi-asserted-by":"publisher","first-page":"6433","DOI":"10.18632\/oncotarget.23942","article-title":"TGF-\u03b22-induced EMT is dampened by inhibition of autophagy and TNF-\u03b1 treatment.","volume":"9","author":"Dash","year":"2018","journal-title":"Oncotarget"},{"key":"B11","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1128\/MCB.00813-13","article-title":"Epigenetic regulation of autophagy by the methyltransferase G9a.","volume":"33","author":"de Narvajas","year":"2013","journal-title":"Mol. Cell Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/j.cell.2007.08.019","article-title":"The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing.","volume":"130","author":"De Santa","year":"2007","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms3916","article-title":"UTX coordinates steroid hormone-mediated autophagy and cell death.","volume":"4","author":"Denton","year":"2013","journal-title":"Nat. Commun."},{"key":"B14","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1038\/nature12313","article-title":"The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy.","volume":"500","author":"F\u00fcllgrabe","year":"2013","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027972","article-title":"Interactions between naive and infected macrophages reduce Mycobacterium tuberculosis viability.","volume":"6","author":"Hartman","year":"2011","journal-title":"PLoS One"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112173","article-title":"Endothelial progenitor cells-secreted extracellular vesicles containing microRNA-93-5p confer protection against sepsis-induced acute kidney injury via the KDM6B\/H3K27me3\/TNF-\u03b1 axis.","volume":"395","author":"He","year":"2020","journal-title":"Exp. Cell Res."},{"key":"B17","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2019103949","article-title":"Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells.","volume":"39","author":"Higashijima","year":"2020","journal-title":"EMBO J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1016\/j.joen.2014.01.031","article-title":"EZH2, a potential regulator of dental pulp inflammation and regeneration.","volume":"40","author":"Hui","year":"2014","journal-title":"J. Endodont."},{"key":"B19","doi-asserted-by":"publisher","first-page":"4031","DOI":"10.1096\/fj.201701483r","article-title":"Histone demethylase JMJD3 regulates fibroblast-like synoviocyte-mediated proliferation and joint destruction in rheumatoid arthritis.","volume":"32","author":"Jia","year":"2018","journal-title":"FASEB. J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/nature16451","article-title":"Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection.","volume":"528","author":"Kimmey","year":"2015","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"6322","DOI":"10.1074\/jbc.m807135200","article-title":"Regulation of autophagy by the p300 acetyltransferase.","volume":"284","author":"Lee","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3374","DOI":"10.1073\/pnas.0712145105","article-title":"A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy.","volume":"105","author":"Lee","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B23","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.joen.2017.12.023","article-title":"FoxO3a regulates inflammation-induced autophagy in odontoblast.","volume":"44","author":"Li","year":"2018","journal-title":"J. Endodont."},{"key":"B24","doi-asserted-by":"publisher","first-page":"12359","DOI":"10.1074\/jbc.ra119.007409","article-title":"Murine macrophage autophagy protects against alcohol-induced liver injury by degrading interferon regulatory factor 1 (IRF1) and removing damaged mitochondria.","volume":"294","author":"Liang","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1126\/science.1217032","article-title":"GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy.","volume":"336","author":"Lin","year":"2012","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1083\/jcb.201008167","article-title":"Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.","volume":"192","author":"Morselli","year":"2011","journal-title":"J. Cell Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"26987","DOI":"10.1074\/jbc.m111.223610","article-title":"p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways.","volume":"286","author":"Mostowy","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1067\/moe.2002.120974","article-title":"Age related odontometric changes of human teeth.","volume":"93","author":"Murray","year":"2002","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.1186\/s13287-017-0506-5","volume":"8","author":"Nakashima","year":"2017","journal-title":"Stem. Cell Res. Ther."},{"key":"B30","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1080\/15548627.2015.1071759","article-title":"Modulation of inflammation by autophagy: consequences for human disease.","volume":"12","author":"Netea-Maier","year":"2016","journal-title":"Autophagy"},{"key":"B31","doi-asserted-by":"publisher","first-page":"39796","DOI":"10.18632\/oncotarget.9290","article-title":"Inhibition of EHMT2\/G9a epigenetically increases the transcription of Beclin-1 via an increase in ROS and activation of NF-\u03baB.","volume":"7","author":"Park","year":"2016","journal-title":"Oncotarget"},{"key":"B32","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-019-1755-2","article-title":"EZH2, JMJD3, and UTX epigenetically regulate hepatic plasticity inducing retro-differentiation and proliferation of liver cells.","volume":"10","author":"Pediconi","year":"2019","journal-title":"Cell Death. Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1080\/15548627.2018.1509608","article-title":"Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy.","volume":"15","author":"Peeters","year":"2019","journal-title":"Autophagy"},{"key":"B34","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1177\/0022034514553815","article-title":"Dual role of autophagy in lipopolysaccharide-induced preodontoblastic cells.","volume":"94","author":"Pei","year":"2015","journal-title":"J. Dent. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s00109-013-1090-5","article-title":"The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia.","volume":"92","author":"Przanowski","year":"2014","journal-title":"J. Mol. Med."},{"key":"B36","first-page":"2749","article-title":"Expression of autophagy-associated proteins in rat dental irreversible pulpitis.","volume":"19","author":"Qi","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.18632\/oncotarget.3354","article-title":"About-face on the metabolic side effects of rapamycin.","volume":"6","author":"Salmon","year":"2015","journal-title":"Oncotarget"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174775","article-title":"Regulation of the JMJD3 (KDM6B) histone demethylase in glioblastoma stem cells by STAT3.","volume":"12","author":"Sherry-Lynes","year":"2017","journal-title":"PLoS One"},{"key":"B39","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms6425","article-title":"An epigenetic switch induced by Shh signalling regulates gene activation during development and medulloblastoma growth.","volume":"5","author":"Shi","year":"2014","journal-title":"Nat. Commun."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1038\/ncb2119","article-title":"Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria.","volume":"12","author":"Singh","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018421","article-title":"p53 interaction with JMJD3 results in its nuclear distribution during mouse neural stem cell differentiation.","volume":"6","author":"Sola","year":"2011","journal-title":"PLoS One"},{"key":"B42","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s12031-016-0796-6","article-title":"Downregulation of KDM4A suppresses the survival of glioma cells by promoting autophagy.","volume":"60","author":"Wang","year":"2016","journal-title":"J. Mol. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1177\/0022034516633639","article-title":"Increased apoptosis of inflamed odontoblasts is associated with CD47 loss.","volume":"95","author":"Wang","year":"2016","journal-title":"J. Dent. Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2428","DOI":"10.1016\/j.bbamcr.2017.08.005","article-title":"Inhibition of H3K4 demethylation induces autophagy in cancer cell lines.","volume":"1864","author":"Wang","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1080\/15548627.2015.1117734","article-title":"Epigenetic regulation of autophagy by the methyltransferase EZH2 through an MTOR-dependent pathway.","volume":"11","author":"Wei","year":"2015","journal-title":"Autophagy"},{"key":"B46","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.yexcr.2017.08.024","article-title":"GSKJ4, an H3K27me3 demethylase inhibitor, effectively suppresses the breast cancer stem cells.","volume":"359","author":"Yan","year":"2017","journal-title":"Exp. Cell Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1007\/s10735-013-9518-3","article-title":"Localization of Beclin1 in mouse developing tooth germs: possible implication of the interrelation between autophagy and apoptosis.","volume":"44","author":"Yang","year":"","journal-title":"J. Mol. Histol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s00418-012-1016-2","article-title":"Autophagy appears during the development of the mouse lower first molar.","volume":"139","author":"Yang","year":"","journal-title":"Histochem. Cell. Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1126\/science.1216990","article-title":"Function and molecular mechanism of acetylation in autophagy regulation.","volume":"336","author":"Yi","year":"2012","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.joen.2016.10.020","article-title":"ASH1L suppresses matrix metalloproteinase through mitogen-activated protein kinase signaling pathway in pulpitis.","volume":"43","author":"Yin","year":"2017","journal-title":"J. Endodont."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.7150\/thno.48679","article-title":"Histone demethylase JMJD3 protects against renal fibrosis by suppressing TGF\u03b2 and Notch signaling and preserving PTEN expression.","volume":"11","author":"Yu","year":"2021","journal-title":"Theranostics"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1038\/cdd.2015.6","article-title":"JMJD3 promotes SAHF formation in senescent WI38 cells by triggering an interplay between demethylation and phosphorylation of RB protein.","volume":"22","author":"Zhao","year":"2015","journal-title":"Cell Death Differ."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.654958\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T08:09:40Z","timestamp":1628496580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.654958\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,9]]},"references-count":52,"alternative-id":["10.3389\/fcell.2021.654958"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.654958","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,9]]},"article-number":"654958"}}