{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:25:48Z","timestamp":1784921148101,"version":"3.55.0"},"reference-count":79,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001364","name":"University of Florida Foundation","doi-asserted-by":"publisher","award":["Research Opportunity Seed Fund Award"],"award-info":[{"award-number":["Research Opportunity Seed Fund Award"]}],"id":[{"id":"10.13039\/100001364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD088006 and HD087528 (to P. S. Cooke), R01 ES025547 (to C. S. Rosenfeld), and R01 HD 096083A (to G. Tuteja)."],"award-info":[{"award-number":["HD088006 and HD087528 (to P. S. Cooke), R01 ES025547 (to C. S. Rosenfeld), and R01 HD 096083A (to G. Tuteja)."]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epigenomes"],"abstract":"<jats:p>Epigenetic modifications regulate normal physiological, as well as pathological processes in various organs, including the uterus and placenta. Both organs undergo dramatic and rapid restructuring that depends upon precise orchestration of events. Epigenetic changes that alter transcription and translation of gene-sets regulate such responses. Histone modifications alter the chromatin structure, thereby affecting transcription factor access to gene promoter regions. Binding of histones to DNA is regulated by addition or removal of subunit methyl and other groups, which can inhibit or stimulate transcription. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2) that catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) and subsequently suppresses transcription of genes bound by such histones. Uterine EZH2 expression exerts a critical role in development and function of this organ with deletion of this gene resulting in uterine hyperplasia and expression of cancer-associated transcripts. Elucidating the roles of EZH2 in uterus and placenta is essential as EZH2 dysregulation is associated with several uterine and placental pathologies. Herein, we discuss EZH2 functions in uterus and placenta, emphasizing its physiological and pathological importance.<\/jats:p>","DOI":"10.3390\/epigenomes4030020","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T09:29:28Z","timestamp":1599038968000},"page":"20","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Roles of the Histone Protein Modifier EZH2 in the Uterus and Placenta"],"prefix":"10.3390","volume":"4","author":[{"given":"Ana M.","family":"Mesa","sequence":"first","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, FL 32610-0144, USA"},{"name":"Grupo de Investigaci\u00f3n en G\u00e9netica, Mejoramiento y Modelaci\u00f3n Animal-GaMMA, Universidad de Antioquia, Medell\u00edn 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4137-3933","authenticated-orcid":false,"given":"Cheryl S.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Bond Life Sciences Center, Department of Biomedical Sciences, Thompson Center for Autism and Neurobehavioral Disorders, Informatics Institute, and Genetics Area Program, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetu","family":"Tuteja","sequence":"additional","affiliation":[{"name":"Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa I.","family":"Medrano","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, FL 32610-0144, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Cooke","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, FL 32610-0144, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nrg1834","article-title":"Inherited epigenetic variation\u2014Revisiting soft inheritance","volume":"7","author":"Richards","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1126\/science.aaf4945","article-title":"Transgenerational inheritance: Models and mechanisms of non\u2013DNA sequence\u2013based inheritance","volume":"354","author":"Miska","year":"2016","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1101\/gad.2037511","article-title":"CpG islands and the regulation of transcription","volume":"25","author":"Deaton","year":"2011","journal-title":"Genes Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1146\/annurev.biochem.77.062706.153223","article-title":"The biology of chromatin remodeling complexes","volume":"78","author":"Clapier","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA methylation and its basic function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3389\/fonc.2019.01091","article-title":"The regulatory roles of non-coding RNAs in angiogenesis and neovascularization from anepigenetic perspective","volume":"9","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fernandes, J.C.R., Acu\u00f1a, S.M., Aoki, J.I., Floeter-Winter, L.M., and Muxel, S.M. (2019). Long non-coding RNAs in the regulation of gene expression: Physiology and disease. Non-Codin. RNA, 5.","DOI":"10.3390\/ncrna5010017"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1126\/science.1063127","article-title":"Translating the histone code","volume":"293","author":"Jenuwein","year":"2001","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nrm.2016.159","article-title":"Histone chaperone networks shaping chromatin function","volume":"18","author":"Hammond","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s12640-014-9508-6","article-title":"A comprehensive view of the epigenetic landscape. Part II: Histone post-translational modification, nucleosome level, and chromatin regulation by ncRNAs","volume":"27","author":"Filip","year":"2015","journal-title":"Neurotox. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e324","DOI":"10.1038\/emm.2017.11","article-title":"Writing, erasing and reading histone lysine methylations","volume":"49","author":"Hyun","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.molcel.2012.11.006","article-title":"Histone lysine methylation dynamics: Establishment, regulation, and biological impact","volume":"48","author":"Black","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3892\/or.2016.5236","article-title":"Non-coding RNAs as regulators in epigenetics","volume":"37","author":"Wei","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.pbiomolbio.2015.02.013","article-title":"Phosphorylation of epigenetic \u201creaders, writers and erasers\u201d: Implications for developmental reprogramming and the epigenetic basis for health and disease","volume":"118","author":"Wang","year":"2015","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1161\/CIRCRESAHA.116.303630","article-title":"Readers, writers, and erasers: Chromatin as the whiteboard of heart disease","volume":"116","author":"Gillette","year":"2015","journal-title":"Circ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1500737","DOI":"10.1126\/sciadv.1500737","article-title":"Regulation of gene transcription by Polycomb proteins","volume":"1","author":"Aranda","year":"2015","journal-title":"Sci. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0092-8674(00)81162-9","article-title":"Polycombing the genome: PcG, trxG, and chromatin silencing","volume":"93","author":"Pirrotta","year":"1998","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1126\/science.1076997","article-title":"Role of histone H3 lysine 27 methylation in Polycomb-group silencing","volume":"298","author":"Cao","year":"2002","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1093\/emboj\/cdg542","article-title":"EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer","volume":"22","author":"Bracken","year":"2003","journal-title":"EMBO J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1177\/1933719115578924","article-title":"H3K27me3 is an epigenetic mark of relevance in endometriosis","volume":"22","author":"Monteiro","year":"2015","journal-title":"Reprod. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1097\/IGC.0b013e318296a265","article-title":"Inhibition of enhancer of zeste homolog 2 (EZH2) expression is associated with decreased tumor cell proliferation, migration, and invasion in endometrial cancer cell lines","volume":"23","author":"Eskander","year":"2013","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/sj.bjc.6605333","article-title":"Expression of EZH2 and Ki-67 in colorectal cancer and associations with treatment response and prognosis","volume":"101","author":"Fluge","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11606","DOI":"10.1073\/pnas.1933744100","article-title":"EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells","volume":"100","author":"Kleer","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1101\/gad.181800.111","article-title":"EZH2 couples pancreatic regeneration to neoplastic progression","volume":"26","author":"Clair","year":"2012","journal-title":"Genes Dev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.tcb.2014.06.005","article-title":"PRC1 complex diversity: Where is it taking us?","volume":"24","author":"Gil","year":"2014","journal-title":"Trends. Cell Biol."},{"key":"ref_26","first-page":"10132","article-title":"Interdependence of PRC1 and PRC2 for recruitment to polycomb response elements","volume":"44","author":"Kahn","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/aps.2013.161","article-title":"EZH2: Biology, disease, and structure-based drug discovery","volume":"35","author":"Tan","year":"2014","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1210\/me.2009-0438","article-title":"Xenoestrogen-induced regulation of EZH2 and histone methylation via estrogen receptor signaling to PI3K\/AKT","volume":"24","author":"Bredfeldt","year":"2010","journal-title":"J. Mol. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6075","DOI":"10.1073\/pnas.1814634116","article-title":"EZH1\/2 function mostly within canonical PRC2 and exhibit proliferation-dependent redundancy that shapes mutational signatures in cancer","volume":"116","author":"Wassef","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.str.2007.08.007","article-title":"Structural basis of EZH2 recognition by EED","volume":"15","author":"Han","year":"2007","journal-title":"Structure"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature09784","article-title":"The Polycomb complex PRC2 and its mark in life","volume":"469","author":"Margueron","year":"2011","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4143\/crt.2014.46.3.209","article-title":"Regulation and role of EZH2 in cancer","volume":"46","author":"Yamaguchi","year":"2014","journal-title":"Cancer Res. Treat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1126\/science.1118947","article-title":"Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3","volume":"310","author":"Cha","year":"2005","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1101\/gad.1983810","article-title":"Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA","volume":"24","author":"Kaneko","year":"2010","journal-title":"Genes Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40364-018-0122-2","article-title":"Epigenetic regulation of cancer progression by EZH2: From biological insights to therapeutic potential","volume":"6","author":"Gan","year":"2018","journal-title":"Biomark. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1128\/MCB.21.13.4330-4336.2001","article-title":"The polycomb-group gene Ezh2 is required for early mouse development","volume":"21","author":"Erhardt","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/gene.20098","article-title":"Cre-mediated recombination in cell lineages that express the progesterone receptor","volume":"41","author":"Soyal","year":"2005","journal-title":"Genesis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.molcel.2008.10.016","article-title":"EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency","volume":"32","author":"Shen","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1152\/physiolgenomics.00098.2019","article-title":"Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation","volume":"52","author":"Mesa","year":"2020","journal-title":"Physiol. Genom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.ajpath.2019.02.016","article-title":"Enhancer of zeste 2 polycomb repressive complex 2 subunit is required for uterine epithelial integrity","volume":"189","author":"Fang","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1158\/1541-7786.MCR-11-0605","article-title":"Environmental estrogens differentially engage the histone methyltransferase EZH2 to increase risk of uterine tumorigenesis","volume":"10","author":"Greathouse","year":"2012","journal-title":"Mol. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1177\/1933719116638186","article-title":"Identification of polycomb group protein EZH2-mediated DNA mismatch repair gene MSH2 in human uterine fibroids","volume":"23","author":"Yang","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fphar.2016.00040","article-title":"Early life adverse environmental exposures increase the risk of uterine fibroid development: Role of epigenetic regulation","volume":"7","author":"Yang","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1095\/biolreprod.115.134924","article-title":"The polycomb group protein EZH2 impairs DNA damage repair gene expression in hman uterine fibroids","volume":"94","author":"Yang","year":"2016","journal-title":"Biol. Reprod."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1177\/1933719117718275","article-title":"Histological and immunohistochemical characterization of the similarity and difference between ovarian endometriomas and deep infiltrating endometriosis","volume":"25","author":"Liu","year":"2018","journal-title":"Reprod. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1093\/biolre\/ioz097","article-title":"The histone methyltransferase EZH2 is required for normal uterine development and function in mice","volume":"101","author":"Nanjappa","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"40402","DOI":"10.18632\/oncotarget.16316","article-title":"Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer","volume":"8","author":"Oki","year":"2017","journal-title":"Oncotarget"},{"key":"ref_48","first-page":"1122","article-title":"HOXA5 inhibits the proliferation and induces the apoptosis of cervical cancer cells via regulation of protein kinase B and p27","volume":"41","author":"Wang","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1093\/molehr\/gau033","article-title":"Uterine epithelial cell proliferation and endometrial hyperplasia: Evidence from a mouse model","volume":"20","author":"Gao","year":"2014","journal-title":"Mol. Hum. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/nature01075","article-title":"The polycomb group protein EZH2 is involved in progression of prostate cancer","volume":"419","author":"Varambally","year":"2002","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Dong, P., Liu, X., Sakuragi, N., and Guo, S.-W. (2017). Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-06920-7"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1172\/JCI200320530","article-title":"Epithelial-mesenchymal transition and its implications for fibrosis","volume":"112","author":"Kalluri","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-mesenchymal transitions in development and disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/biolre\/ioy030","article-title":"Effects of histone methyltransferase inhibition in endometriosis\u2020","volume":"99","author":"Young","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_55","first-page":"7191","article-title":"Expression of EZH2 in endometrial carcinoma and its effects on proliferation and invasion of endometrial carcinoma cells","volume":"14","author":"Gu","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40661-017-0052-y","article-title":"EZH2 inhibition in ARID1A mutated clear cell and endometrioid ovarian and endometrioid endometrial cancers","volume":"4","author":"Alldredge","year":"2017","journal-title":"Gynecol. Oncol. Res. Pract."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nm.4036","article-title":"Targeting EZH2 in cancer","volume":"22","author":"Kim","year":"2016","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6542","DOI":"10.1038\/onc.2017.262","article-title":"EZH2-mediated upregulation of ROS1 oncogene promotes oral cancer metastasis","volume":"36","author":"Shih","year":"2017","journal-title":"Oncogene"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/cdd.2009.162","article-title":"Polycomb protein EZH2 regulates E2F1-dependent apoptosis through epigenetically modulating Bim expression","volume":"17","author":"Wu","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1038\/s41598-019-39122-4","article-title":"Genome-wide expression analysis reveals six contravened targets of EZH2 associated with breast cancer patient survival","volume":"9","author":"Kumari","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1016\/j.celrep.2018.11.035","article-title":"Polycomb- and methylation-independent roles of EZH2 as a transcription activator","volume":"25","author":"Kim","year":"2018","journal-title":"Cell Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5020","DOI":"10.7150\/thno.34700","article-title":"Overcoming EZH2 inhibitor resistance by taxane in PTEN-mutated cancer","volume":"9","author":"Ma","year":"2019","journal-title":"Theranostics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ajog.2010.08.009","article-title":"The \u201cGreat Obstetrical Syndromes\u201d are associated with disorders of deep placentation","volume":"204","author":"Brosens","year":"2011","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3389\/fendo.2018.00570","article-title":"Regulation of placental development and its impact on fetal growth-new insights from mouse models","volume":"9","author":"Woods","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"dev163428","DOI":"10.1242\/dev.163428","article-title":"Development of the human placenta","volume":"146","author":"Turco","year":"2019","journal-title":"Development"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/biolre\/ioy049","article-title":"Hemochorial placentation: Development, function, and adaptations","volume":"99","author":"Soares","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/35080570","article-title":"Placental development: Lessons from mouse mutants","volume":"2","author":"Rossant","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-04992-1","article-title":"Placental H3K27me3 establishes female resilience to prenatal insults","volume":"9","author":"Nugent","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5169","DOI":"10.1073\/pnas.1300065110","article-title":"O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development","volume":"110","author":"Howerton","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/dvg.20276","article-title":"Expression of Cre recombinase in early diploid trophoblast cells of the mouse placenta","volume":"45","author":"Wenzel","year":"2007","journal-title":"Genesis"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/neuro.08.019.2009","article-title":"Prenatal stress, glucocorticoids and the programming of adult disease","volume":"3","author":"Cottrell","year":"2009","journal-title":"Front. Behav. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1210\/en.2008-1100","article-title":"Altered placental function of 11beta-hydroxysteroid dehydrogenase 2 knockout mice","volume":"150","author":"Wyrwoll","year":"2009","journal-title":"Endocrinology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/apha.12187","article-title":"Foetal and placental 11\u03b2-HSD2: A hub for developmental programming","volume":"210","author":"Cottrell","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7578","DOI":"10.1074\/jbc.M116.765800","article-title":"A repressive role of enhancer of zeste homolog 2 in 11\u03b2-hydroxysteroid dehydrogenase type 2 expression in the human placenta","volume":"292","author":"Zuo","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e3104","DOI":"10.1038\/cddis.2017.503","article-title":"The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic suppression of RND3","volume":"8","author":"Xu","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1111\/jcmm.13405","article-title":"The long non-coding RNA PVT1 represses ANGPTL4 transcription through binding with EZH2 in trophoblast cell","volume":"22","author":"Xu","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.omtn.2018.12.011","article-title":"The attenuation of trophoblast invasion caused by the downregulation of EZH2 is involved in the pathogenesis of human recurrent miscarriage","volume":"14","author":"Lv","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Huppertz, B. (2019). Traditional and new routes of trophoblast invasion and their implications for pregnancy diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010289"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.stem.2017.11.004","article-title":"Derivation of human trophoblast stem cells","volume":"22","author":"Okae","year":"2018","journal-title":"Cell Stem Cell"}],"container-title":["Epigenomes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4655\/4\/3\/20\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:06:01Z","timestamp":1760177161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4655\/4\/3\/20"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,2]]},"references-count":79,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["epigenomes4030020"],"URL":"https:\/\/doi.org\/10.3390\/epigenomes4030020","relation":{},"ISSN":["2075-4655"],"issn-type":[{"value":"2075-4655","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,2]]}}}