TY - JOUR
T1 - Passive and active DNA methylation and the interplay with genetic variation in gene regulation
AU - Gutierrez-Arcelus, Maria
AU - Lappalainen, Tuuli
AU - Montgomery, Stephen B.
AU - Buil, Alfonso
AU - Ongen, Halit
AU - Yurovsky, Alisa
AU - Bryois, Julien
AU - Giger, Thomas
AU - Romano, Luciana
AU - Planchon, Alexandra
AU - Falconnet, Emilie
AU - Bielser, Deborah
AU - Gagnebin, Maryline
AU - Padioleau, Ismael
AU - Borel, Christelle
AU - Letourneau, Audrey
AU - Makrythanasis, Periklis
AU - Guipponi, Michel
AU - Gehrig, Corinne
AU - Antonarakis, Stylianos E.
AU - Dermitzakis, Emmanouil T.
PY - 2013/6/4
Y1 - 2013/6/4
N2 - 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. Copyright Gutierrez-Arcelus et al.
AB - 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. Copyright Gutierrez-Arcelus et al.
UR - https://www.scopus.com/pages/publications/84879055641
U2 - 10.7554/eLife.00523
DO - 10.7554/eLife.00523
M3 - Article
C2 - 23755361
AN - SCOPUS:84879055641
SN - 2050-084X
VL - 2013
JO - eLife
JF - eLife
IS - 2
M1 - e00523
ER -