Abstract
BackgroundEpigenomic 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.ResultsWe 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.ConclusionsQuantitative 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-015-0019-3) contains supplementary material, which is available to authorized users.
Highlights
Epigenomic studies on humans and model species have revealed substantial inter-individual vari‐ ation in histone modification profiles
We report on the extent and pattern of intra-species quantitative variation of histone modifications in the epigenome of S. cerevisiae
Epigenomic profiling of five histone modification marks was performed at singlenucleosome resolution, in biological replicates
Summary
Epigenomic studies on humans and model species have revealed substantial inter-individual vari‐ ation in histone modification profiles. Filleton et al Epigenetics & Chromatin (2015) 8:26 various timescales, they differ between cell types and their presence or absence can result from a response to environmental conditions. Comparing epigenomes is more challenging than population genomics, because there is more to read than a four nucleotide sequence and the ‘text’ differs quantitatively rather than qualitatively, between individuals, and according to various factors. In this regard, yeast offers the possibility to study epigenomic variation in a simplified context, where the complexity of multiple cell types is avoided and environmental conditions can be controlled. We use the term ‘epigenome’ to describe the genomic profile of one or several chromatin marks, and the term ‘epi-polymorphism’ to describe variation in the epigenome, regardless of the possible epigenetic maintenance of these marks
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