eLife (Jun 2013)
Passive and active DNA methylation and the interplay with genetic variation in gene regulation
- Maria Gutierrez-Arcelus,
- Tuuli Lappalainen,
- Stephen B Montgomery,
- Alfonso Buil,
- Halit Ongen,
- Alisa Yurovsky,
- Julien Bryois,
- Thomas Giger,
- Luciana Romano,
- Alexandra Planchon,
- Emilie Falconnet,
- Deborah Bielser,
- Maryline Gagnebin,
- Ismael Padioleau,
- Christelle Borel,
- Audrey Letourneau,
- Periklis Makrythanasis,
- Michel Guipponi,
- Corinne Gehrig,
- Stylianos E Antonarakis,
- Emmanouil T Dermitzakis
Affiliations
- Maria Gutierrez-Arcelus
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- Tuuli Lappalainen
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- Stephen B Montgomery
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Departments of Pathology and Genetics, Stanford University, Stanford, United States
- Alfonso Buil
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- Halit Ongen
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- Alisa Yurovsky
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- Julien Bryois
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- Thomas Giger
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Luciana Romano
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- Alexandra Planchon
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- Emilie Falconnet
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Deborah Bielser
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Maryline Gagnebin
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Ismael Padioleau
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- Christelle Borel
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Audrey Letourneau
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Periklis Makrythanasis
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Michel Guipponi
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Corinne Gehrig
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Stylianos E Antonarakis
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland
- Emmanouil T Dermitzakis
- Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Geneva, Switzerland; Swiss Institute of Bioinformatics, Geneva, Switzerland
- DOI
- https://doi.org/10.7554/eLife.00523
- Journal volume & issue
-
Vol. 2
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.
Keywords