title: Genetic modifiers of chromatin acetylation antagonize the reprogramming of epi-polymorphisms.
abstract: Natural populations are known to differ not only in DNA but also in their chromatin-associated epigenetic marks. When such inter-individual epigenomic differences (or "epi-polymorphisms") are observed, their stability is usually not known: they may or may not be reprogrammed over time or upon environmental changes. In addition, their origin may be purely epigenetic, or they may result from regulatory variation encoded in the DNA. Studying epi-polymorphisms requires, therefore, an assessment of their nature and stability. Here we estimate the stability of yeast epi-polymorphisms of chromatin acetylation, and we provide a genome-by-epigenome map of their genetic control. A transient epi-drug treatment was able to reprogram acetylation variation at more than one thousand nucleosomes, whereas a similar amount of variation persisted, distinguishing "labile" from "persistent" epi-polymorphisms. Hundreds of genetic loci underlied acetylation variation at 2,418 nucleosomes either locally (in cis) or distantly (in trans), and this genetic control overlapped only partially with the genetic control of gene expression. Trans-acting regulators were not necessarily associated with genes coding for chromatin modifying enzymes. Strikingly, "labile" and "persistent" epi-polymorphisms were associated with poor and strong genetic control, respectively, showing that genetic modifiers contribute to persistence. These results estimate the amount of natural epigenomic variation that can be lost after transient environmental exposures, and they reveal the complex genetic architecture of the DNA-encoded determinism of chromatin epi-polymorphisms. Our observations provide a basis for the development of population epigenetics.
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, Université de Lyon, Lyon, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Abraham
authors.forename: Muniyandi
authors.initials: M
authors.lastname: Nagarajan
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Veyrieras
authors.forename: Hélène
authors.initials: H
authors.lastname: Bottin
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.forename: Gaël
authors.initials: G
authors.lastname: Yvert
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D005828:Genetics, Population; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D011495:Histone-Lysine N-Methyltransferase