{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T14:57:51Z","timestamp":1764946671672,"version":"3.46.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"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. Epigenet. Epigenom."],"abstract":"\n Introduction<\/jats:title>\n Preterm birth (PTB), a leading cause of neonatal morbidity and mortality, arises from complex maternal-fetal interactions with multifactorial origins. Emerging evidence suggests that epigenetic dysregulation may mediate these interactions. This study aimed to identify DNA methylation changes associated with PTB to uncover potential biomarkers and underlying mechanisms.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We employed long-read sequencing to profile genome-wide DNA methylation followed by gene ontology and pathway enrichment analysis in matched maternal peripheral blood and neonatal cord blood from 15 preterm and 7 full-term deliveries (mother\u2013infant pairs).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 1,151 significantly differentially methylated regions (DMRs) and 25,336 differentially methylated loci (DMLs) were identified across maternal and neonatal blood samples. In maternal blood from PTB cases, the most significantly hypermethylated genes were\n MED38<\/jats:italic>\n ,\n PSMB11<\/jats:italic>\n , and\n WNT7B<\/jats:italic>\n , whereas\n EXTL3<\/jats:italic>\n and\n MMP9<\/jats:italic>\n were among the most hypomethylated. Additionally, the promoters of\n VWA5A<\/jats:italic>\n ,\n EIF4E3<\/jats:italic>\n ,\n ZNF571<\/jats:italic>\n , and\n COPB2<\/jats:italic>\n exhibited significant hypermethylation, while those of\n SIRPB1<\/jats:italic>\n and\n TNFRSF19<\/jats:italic>\n showed hypomethylation. In neonatal cord blood from PTB cases, the most significantly hypermethylated genes were\n LOC401478<\/jats:italic>\n ,\n ISG20<\/jats:italic>\n ,\n LMTK3<\/jats:italic>\n ,\n TCAF2<\/jats:italic>\n , and\n COL4A2<\/jats:italic>\n , whereas\n EXTL3<\/jats:italic>\n and\n MMP9<\/jats:italic>\n were among the most hypomethylated. Promoters of\n DKK3<\/jats:italic>\n ,\n CELF2<\/jats:italic>\n , and\n IFI35<\/jats:italic>\n were notably hypermethylated, whereas\n ALOX12<\/jats:italic>\n and\n CLBA1<\/jats:italic>\n were among the most hypomethylated. Enrichment analysis revealed that these epigenetic alterations impact critical developmental, immune, and neuroendocrine pathways, including Wnt signaling, calcium signaling, MAPK, oxytocin signaling, and neuroactive ligand-receptor interaction. Comparative analysis identified 120 overlapping DMLs, with 91 hypermethylated and 28 hypomethylated consistently across maternal and neonatal samples, including\n DPPA3<\/jats:italic>\n ,\n ABCA1<\/jats:italic>\n , and\n GKN1<\/jats:italic>\n . In contrast, 20,240 and 4,770 DMLs were unique to cord and peripheral blood, respectively. Additionally, 14 overlapping DMRs were mapped to genes such as\n PLD5<\/jats:italic>\n ,\n FBXO40<\/jats:italic>\n ,\n GMNC<\/jats:italic>\n ,\n HHIP<\/jats:italic>\n ,\n CLEC18B<\/jats:italic>\n , and\n LHX1<\/jats:italic>\n , exhibiting non-random chromosomal clustering. Enrichment analysis of these shared DMRs revealed significant involvement in developmental processes, including skeletal morphogenesis, axis patterning, and fibroblast growth factor signaling, indicating convergence on core regulatory pathways in PTB.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This is the first dual-tissue PTB study using long-read methylation profiling. Our results reveal distinct and shared epigenetic signatures in maternal and neonatal compartments, offering insights into the molecular etiology of PTB and potential biomarkers for early detection and therapeutic intervention.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/freae.2025.1644521","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T14:55:06Z","timestamp":1764946506000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic profiling of preterm birth: a dual-tissue methylation patterns using long-read sequencing"],"prefix":"10.3389","volume":"3","author":[{"given":"BalaSubramani Gattu","family":"Linga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faisal E.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleem","family":"Razzaq","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muthanna","family":"Samara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jameela","family":"Roshanuddin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hind H.","family":"Adi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aseel","family":"Al-Dewik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayla J.","family":"Ahmedoglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rand","family":"Hamdan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amal E. 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