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CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development

Please always quote using this URN: urn:nbn:de:bvb:20-opus-186936
  • Normal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays. Sites showing genome-wide significant correlation with gestational age were compared to a publicly available data set from gestational weeks 3-26. Altogether, we identified 2016 matchingNormal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays. Sites showing genome-wide significant correlation with gestational age were compared to a publicly available data set from gestational weeks 3-26. Altogether, we identified 2016 matching developmentally regulated differentially methylated positions (m-dDMPs): 1767 m-dDMPs were hypermethylated and 1149 hypomethylated during fetal development. M-dDMPs are underrepresented in CpG islands and gene promoters, and enriched in gene bodies. They appear to cluster in certain chromosome regions. M-dDMPs are significantly enriched in autism-associated genes and CpGs. Our results promote the idea that reduced methylation dynamics during fetal brain development may predispose to autism. In addition, m-dDMPs are enriched in genes with human-specific brain expression patterns and/or histone modifications. Collectively, we defined a subset of dDMPs exhibiting constant methylation changes from early to late pregnancy. The same epigenetic mechanisms involving methylation changes in cis-regulatory regions may have been adopted for human brain evolution and ontogeny.show moreshow less

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Metadaten
Author: Eberhard Schneider, Marcus Dittrich, Julia Böck, Indrajit Nanda, Tobias Müller, Larissa Seidmann, Tim Tralau, Danuta Galetzka, Nady El Hajj, Thomas Haaf
URN:urn:nbn:de:bvb:20-opus-186936
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Humangenetik
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Gene
Year of Completion:2016
Volume:592
Issue:1
Pagenumber:110-118
Source:Gene (2016) 592:1, 110-118. https://doi.org/10.1016/j.gene.2016.07.058
DOI:https://doi.org/10.1016/j.gene.2016.07.058
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Autism; Autism spectrum disorders; DNA methylation; DNA methylation dynamics; Environment; Epigenetics; Fetal brain development; Frontal cortex; Gene-expression; Genome; Human prefrontal cortex; Methylome; Patterns; Schizophrenia; Transcription
Release Date:2020/05/28
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International