Fluctuations in chromatin state at regulatory loci occur spontaneously under relaxed selection and are associated with epigenetically inherited variation in C. elegans gene expression

• Published in: PLoS genetics Vol. 19; no. 3; p. e1010647
• Main Authors: Wilson, Rachel, Le Bourgeois, Maxime, Perez, Marcos, Sarkies, Peter
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.03.2023; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Biology and Life Sciences; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Chromatin; Chromatin - genetics; Comparative analysis; Control; DNA Methylation; DNA sequencing; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Gene Expression; Gene mutations; Genes; Genetic aspects; Health aspects; Heredity; Identification and classification; Laboratories; MicroRNAs; Mutation; Nucleotide sequence; Nucleotide sequencing; Proteins; Regulatory sequences; Research and Analysis Methods; RNA; RNA polymerase; United Kingdom
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1010647

Some epigenetic information can be transmitted between generations without changes in the underlying DNA sequence. Changes in epigenetic regulators, termed epimutations, can occur spontaneously and be propagated in populations in a manner reminiscent of DNA mutations. Small RNA-based epimutations occur in C. elegans and persist for around 3-5 generations on average. Here, we explored whether chromatin states also undergo spontaneous change and whether this could be a potential alternative mechanism for transgenerational inheritance of gene expression changes. We compared the chromatin and gene expression profiles at matched time points from three independent lineages of C. elegans propagated at minimal population size. Spontaneous changes in chromatin occurred in around 1% of regulatory regions each generation. Some were heritable epimutations and were significantly enriched for heritable changes in expression of nearby protein-coding genes. Most chromatin-based epimutations were short-lived but a subset had longer duration. Genes subject to long-lived epimutations were enriched for multiple components of xenobiotic response pathways. This points to a possible role for epimutations in adaptation to environmental stressors.