{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:51:31Z","timestamp":1791179491613,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Successful human pregnancy depends on the precise spatio-temporal orchestration of trophoblast lineages to establish a functional feto-maternal interface. While deoxyribonucleic acid (DNA) methyltransferases (DNMTs) are recognized as core drivers of epigenetic programming, emerging evidence reveals that they are not merely passive transcriptional silencers, but also dynamic architectural coordinators of placental morphogenesis. This work presents the roles of maintenance (DNMT1) and de novo (DNMT3A, DNMT3B) methyltransferases in dictating the precise timing of trophoblast fate transitions. During trophoblast fusion, a coordinated downregulation of the DNMT machinery permits the localized demethylation and activation of vital fusogenic networks. Conversely, extravillous trophoblast invasion requires active DNMT-mediated hypermethylation to silence anti-invasive genes. Disruptions in these tightly synchronized epigenetic pulses trigger lineage-specific malfunctions that are associated with the pathogenesis of gestational disorders such as preeclampsia and fetal growth restriction. Despite these insights, fundamental knowledge gaps remain unaddressed. For instance, how DNMT expression and enzymatic assembly adapt to localized physical forces at the feto-maternal interface remains unknown. It is also unclear whether DNMTs exhibit non-canonical and non-enzymatic structural scaffolding properties during early implantation, and whether functional DNMT machinery is actively encapsulated within placenta-derived extracellular vesicles to cross the fetal blood\u2013brain barrier and alter distant fetal neurodevelopment. Resolving these profound mechano-chemical, structural, and systemic knowledge gaps is essential to deciphering early human development and identifying novel therapeutic targets in feto-maternal medicine.<\/jats:p>","DOI":"10.1093\/biolre\/ioag203","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:21:55Z","timestamp":1789755715000},"source":"Crossref","is-referenced-by-count":0,"title":["DNA methyltransferases in trophoblast differentiation: extant knowledge and emerging paradigms"],"prefix":"10.1093","author":[{"given":"Enoch Appiah","family":"Adu-Gyamfi","sequence":"first","affiliation":[{"name":"Department of Biology, University of Wisconsin-Stout , 410 10th Avenue E, Menomonie, Dunn County, Wisconsin ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2026100501015520200_ref1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nrg.2017.80","article-title":"The DNA methyltransferase family: a versatile toolkit for epigenetic regulation","volume":"19","author":"Lyko","year":"2018","journal-title":"Nat Rev Genet"},{"key":"2026100501015520200_ref2","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1101\/gad.234294.113","article-title":"DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos","volume":"28","author":"Messerschmidt","year":"2014","journal-title":"Genes Dev"},{"key":"2026100501015520200_ref3","doi-asserted-by":"crossref","first-page":"617","DOI":"10.3390\/genes9120617","article-title":"Mechanisms of DNA methyltransferase recruitment in mammals","volume":"9","author":"Laisn\u00e9","year":"2018","journal-title":"Genes (Basel)"},{"key":"2026100501015520200_ref4","first-page":"395","article-title":"Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2","volume":"2006","author":"Goll","year":"1979","journal-title":"Science"},{"key":"2026100501015520200_ref5","doi-asserted-by":"publisher","first-page":"48350","DOI":"10.1074\/jbc.M403427200","article-title":"The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites","volume":"279","author":"Hermann","year":"2004","journal-title":"J Biol Chem"},{"key":"2026100501015520200_ref6","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S0092-8674(00)81656-6","article-title":"DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development","volume":"99","author":"Okano","year":"1999","journal-title":"Cell"},{"key":"2026100501015520200_ref7","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/ncomms2562","article-title":"UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9","volume":"4","author":"Liu","year":"2013","journal-title":"Nat Commun"},{"key":"2026100501015520200_ref8","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/nature02633","article-title":"Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting","volume":"429","author":"Kaneda","year":"2004","journal-title":"Nature"},{"key":"2026100501015520200_ref9","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41467-023-36019-9","article-title":"Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B","volume":"14","author":"Andrews","year":"2023","journal-title":"Nat Commun"},{"key":"2026100501015520200_ref10","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41586-019-1825-8","article-title":"Multi-omics profiling of mouse gastrulation at single-cell resolution","volume":"576","author":"Argelaguet","year":"2019","journal-title":"Nature"},{"key":"2026100501015520200_ref11","doi-asserted-by":"publisher","volume-title":"Dnmt3L Cooperates with the Dnmt3 Family of De Novo DNA Methyltransferases to Establish Maternal Imprints in Mice. 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