title: The complex pattern of epigenomic variation between natural yeast strains at single-nucleosome resolution.
abstract: BACKGROUND
  Epigenomic studies on humans and model species have revealed substantial inter-individual variation in histone modification profiles. However, the pattern of this variation has not been precisely characterized, particularly regarding which genomic features are enriched for variability and whether distinct histone marks co-vary synergistically. Yeast allows us to investigate intra-species variation at high resolution while avoiding other sources of variation, such as cell type or subtype.
  
  
  RESULTS
  We profiled histone marks H3K4me3, H3K9ac, H3K14ac, H4K12ac and H3K4me1 in three unrelated wild strains of Saccharomyces cerevisiae at single-nucleosome resolution and analyzed inter-strain differences statistically. All five marks varied significantly at specific loci, but to different extents. The number of nucleosomes varying for a given mark between two strains ranged from 20 to several thousands; +1 nucleosomes were significantly less subject to variation. Genes with highly evolvable or responsive expression showed higher variability; however, the variation pattern could not be explained by known transcriptional differences between the strains. Synergistic variation of distinct marks was not systematic, with surprising differences between functionally related H3K9ac and H3K14ac. Interestingly, H3K14ac differences that persisted through transient hyperacetylation were supported by H3K4me3 differences, suggesting stabilization via cross talk.
  
  
  CONCLUSIONS
  Quantitative variation of histone marks among S. cerevisiae strains is abundant and complex. Its relation to functional characteristics is modular and seems modest, with partial association with gene expression divergences, differences between functionally related marks and partial co-variation between marks that may confer stability. Thus, the specific context of studies, such as which precise marks, individuals and genomic loci are investigated, is primordial in population epigenomics studies. The complexity found in this pilot survey in yeast suggests that high complexity can be anticipated among higher eukaryotes, including humans.
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, Université de Lyon, 46 Allée d'Italie, 69007 Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Filleton
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, Université de Lyon, 46 Allée d'Italie, 69007 Lyon, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Chuffart
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, Université de Lyon, 46 Allée d'Italie, 69007 Lyon, France ; Department of Genomic Science, School of Biological Sciences, Central University of Kerala, Kerala, India.
authors.forename: Muniyandi
authors.initials: M
authors.lastname: Nagarajan
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, Université de Lyon, 46 Allée d'Italie, 69007 Lyon, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bottin-Duplus
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, Université de Lyon, 46 Allée d'Italie, 69007 Lyon, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Yvert
keywords: Ecology; Epi-allele; Epi-polymorphism; Epigenomics; Evolution; Histone modification; Natural strains; Yeast