Natural cryptic variation in epigenetic modulation of an embryonic gene regulatory network.

TitleNatural cryptic variation in epigenetic modulation of an embryonic gene regulatory network.
Publication TypeJournal Article
Year of Publication2020
AuthorsEwe CKiang, Cleuren YNTorres, Flowers SE, Alok G, Snell RG, Rothman JH
JournalProc Natl Acad Sci U S A
Date Published2020 06 16
KeywordsAnimals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, DNA-Binding Proteins, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Histone-Lysine N-Methyltransferase, Transcription Factors

Gene regulatory networks (GRNs) that direct animal embryogenesis must respond to varying environmental and physiological conditions to ensure robust construction of organ systems. While GRNs are evolutionarily modified by natural genomic variation, the roles of epigenetic processes in shaping plasticity of GRN architecture are not well understood. The endoderm GRN in is initiated by the maternally supplied SKN-1/Nrf2 bZIP transcription factor; however, the requirement for SKN-1 in endoderm specification varies widely among distinct wild isotypes, owing to rapid developmental system drift driven by accumulation of cryptic genetic variants. We report here that heritable epigenetic factors that are stimulated by transient developmental diapause also underlie cryptic variation in the requirement for SKN-1 in endoderm development. This epigenetic memory is inherited from the maternal germline, apparently through a nuclear, rather than cytoplasmic, signal, resulting in a parent-of-origin effect (POE), in which the phenotype of the progeny resembles that of the maternal founder. The occurrence and persistence of POE varies between different parental pairs, perduring for at least 10 generations in one pair. This long-perduring POE requires piwi-interacting RNA (piRNA) function and the germline nuclear RNA interference (RNAi) pathway, as well as MET-2 and SET-32, which direct histone H3K9 trimethylation and drive heritable epigenetic modification. Such nongenetic cryptic variation may provide a resource of additional phenotypic diversity through which adaptation may facilitate evolutionary changes and shape developmental regulatory systems.

Alternate JournalProc Natl Acad Sci U S A
PubMed ID32482879
PubMed Central IDPMC7306808
Grant ListP40 OD010440 / OD / NIH HHS / United States
R01 HD081266 / HD / NICHD NIH HHS / United States
R01 HD082347 / HD / NICHD NIH HHS / United States