Autor según el artículo: Ondičová M; Irwin RE; Thursby SJ; Hilman L; Caffrey A; Cassidy T; McLaughlin M; Lees-Murdock DJ; Ward M; Murphy M; Lamers Y; Pentieva K; McNulty H; Walsh CP
Departamento: Ciències Mèdiques Bàsiques
Autor/es de la URV: Murphy, Michelle
Palabras clave: deficiency dna methylation dnmt3b expression folate mecp2 mutation neurodevelopment proliferation supplementation Dna methylation Folic acid Neurodevelopment Primary cilium
Resumen: We previously showed that continued folic acid (FA) supplementation beyond the first trimester of pregnancy appears to have beneficial effects on neurocognitive performance in children followed for up to 11 years, but the biological mechanism for this effect has remained unclear. Using samples from our randomized controlled trial of folic acid supplementation in second and third trimester (FASSTT), where significant improvements in cognitive and psychosocial performance were demonstrated in children from mothers supplemented in pregnancy with 400 µg/day FA compared with placebo, we examined methylation patterns from cord blood (CB) using the EPIC array which covers approximately 850,000 cytosine-guanine (CG) sites across the genome. Genes showing significant differences were verified using pyrosequencing and mechanistic approaches used in vitro to determine effects on transcription.FA supplementation resulted in significant differences in methylation, particularly at brain-related genes. Further analysis showed these genes split into two groups. In one group, which included the CES1 gene, methylation changes at the promoters were important for regulating transcription. We also identified a second group which had a characteristic bimodal profile, with low promoter and high gene body (GB) methylation. In the latter, loss of methylation in the GB is linked to decreases in transcription: this group included the PRKAR1B/HEATR2 genes and the dopamine receptor regulator PDE4C. Overall, methylation in CB also showed good correlation with methylation profiles seen in a published data set of late gestation foetal brain samples.We show here clear alterations in DNA methylation at specific classes of neurodevelopmental genes in the same cohort of children, born to FA-supplemented mothers, who previously showed improved cognitive and psychosocial performance. Our results show measurable differences at neural genes which are important for transcriptional regulation and add to the supporting evidence for continued FA supplementation throughout later gestation. This trial was registered on 15 May 2013 at www.isrctn.com as ISRCTN19917787.© 2022. The Author(s).
Áreas temáticas: Biotecnología Ciências biológicas i Ciências biológicas ii Developmental biology General medicine Genetics Genetics & heredity Genetics (clinical) Medicina i Molecular biology Odontología Oncology
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: michelle.murphy@urv.cat
Identificador del autor: 0000-0002-6304-6204
Fecha de alta del registro: 2024-01-13
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-022-01282-y
Referencia al articulo segun fuente origial: Clinical Epigenetics. 14 (1): 63-63
Referencia de l'ítem segons les normes APA: Ondičová M; Irwin RE; Thursby SJ; Hilman L; Caffrey A; Cassidy T; McLaughlin M; Lees-Murdock DJ; Ward M; Murphy M; Lamers Y; Pentieva K; McNulty H; Wa (2022). Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms. Clinical Epigenetics, 14(1), 63-63. DOI: 10.1186/s13148-022-01282-y
URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/
DOI del artículo: 10.1186/s13148-022-01282-y
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2022
Tipo de publicación: Journal Publications
Repositori URV