title: Passive and active DNA methylation and the interplay with genetic variation in gene regulation.
abstract: DNA methylation is an essential epigenetic mark whose role in gene regulation and its dependency on genomic sequence and environment are not fully understood. In this study we provide novel insights into the mechanistic relationships between genetic variation, DNA methylation and transcriptome sequencing data in three different cell-types of the GenCord human population cohort. We find that the association between DNA methylation and gene expression variation among individuals are likely due to different mechanisms from those establishing methylation-expression patterns during differentiation. Furthermore, cell-type differential DNA methylation may delineate a platform in which local inter-individual changes may respond to or act in gene regulation. We show that unlike genetic regulatory variation, DNA methylation alone does not significantly drive allele specific expression. Finally, inferred mechanistic relationships using genetic variation as well as correlations with TF abundance reveal both a passive and active role of DNA methylation to regulatory interactions influencing gene expression. DOI:http://dx.doi.org/10.7554/eLife.00523.001.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland [corrected]; Swiss Institute of Bioinformatics, Geneva, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Gutierrez-Arcelus
authors.forename: Tuuli
authors.initials: T
authors.lastname: Lappalainen
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Montgomery
authors.forename: Alfonso
authors.initials: A
authors.lastname: Buil
authors.forename: Halit
authors.initials: H
authors.lastname: Ongen
authors.forename: Alisa
authors.initials: A
authors.lastname: Yurovsky
authors.forename: Julien
authors.initials: J
authors.lastname: Bryois
authors.forename: Thomas
authors.initials: T
authors.lastname: Giger
authors.forename: Luciana
authors.initials: L
authors.lastname: Romano
authors.forename: Alexandra
authors.initials: A
authors.lastname: Planchon
authors.forename: Emilie
authors.initials: E
authors.lastname: Falconnet
authors.forename: Deborah
authors.initials: D
authors.lastname: Bielser
authors.forename: Maryline
authors.initials: M
authors.lastname: Gagnebin
authors.forename: Ismael
authors.initials: I
authors.lastname: Padioleau
authors.forename: Christelle
authors.initials: C
authors.lastname: Borel
authors.forename: Audrey
authors.initials: A
authors.lastname: Letourneau
authors.forename: Periklis
authors.initials: P
authors.lastname: Makrythanasis
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
authors.forename: Corinne
authors.initials: C
authors.lastname: Gehrig
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Emmanouil T
authors.initials: ET
authors.lastname: Dermitzakis
mesh_terms: D000483:Alleles; D002478:Cells, Cultured; D019175:DNA Methylation; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D007231:Infant, Newborn; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors
keywords: Human; epigenetics; gene regulation; genome variation; methylation