title: Limited Contribution of DNA Methylation Variation to Expression Regulation in Arabidopsis thaliana.
abstract: The extent to which epigenetic variation affects complex traits in natural populations is not known. We addressed this question using transcriptome and DNA methylation data from a sample of 135 sequenced A. thaliana accessions. Across individuals, expression was significantly associated with cis-methylation for hundreds of genes, and many of these associations remained significant after taking SNP effects into account. The pattern of correlations differed markedly between gene body methylation and transposable element methylation. The former was usually positively correlated with expression, and the latter usually negatively correlated, although exceptions were found in both cases. Finally, we developed graphical models of causality that adapt to a sample with heavy population structure, and used them to show that while methylation appears to affect gene expression more often than expression affects methylation, there is also strong support for both being independently controlled. In conclusion, although we find clear evidence for epigenetic regulation, both the number of loci affected and the magnitude of the effects appear to be small compared to the effect of SNPs.
authors.affiliation: Gregor Mendel Institute, Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria.|Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States.
authors.forename: Dazhe
authors.identifier: 0000-0001-7439-2498
authors.initials: D
authors.lastname: Meng
authors.affiliation: Gregor Mendel Institute, Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria.
authors.forename: Manu
authors.initials: M
authors.lastname: Dubin
authors.affiliation: Gregor Mendel Institute, Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria.|Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, United States.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Osborne
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stegle
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, United States.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Clark
authors.affiliation: Gregor Mendel Institute, Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria.|Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States.
authors.forename: Magnus
authors.identifier: 0000-0001-7178-9748
authors.initials: M
authors.lastname: Nordborg
mesh_terms: D017360:Arabidopsis / Q000235:genetics* / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics; D060565:Argonaute Proteins / Q000235:genetics; D002874:Chromosome Mapping; D003198:Computer Simulation; D019175:DNA Methylation; D004251:DNA Transposable Elements; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D018506:Gene Expression Regulation, Plant; D017343:Genes, Plant; D018745:Genome, Plant; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D059467:Transcriptome
chemical_list: C471209:AGO4 protein, Arabidopsis; D029681:Arabidopsis Proteins; D060565:Argonaute Proteins; D004251:DNA Transposable Elements