Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance.
Sjoberg-Herrera, Marcela K
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Kazachenka, A., Bertozzi, T., Sjoberg-Herrera, M. K., Walker, N., Gardner, J., Gunning, R., Pahita, E., et al. (2018). Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance.. Cell, 175 (5), 1259-1271.e13. https://doi.org/10.1016/j.cell.2018.09.043
Generally repressed by epigenetic mechanisms, retrotransposons represent around 40% of the murine genome. At the Agouti viable yellow (Avy) locus, an endogenous retrovirus (ERV) of the intracisternal A particle (IAP) class retrotransposed upstream of the agouti coat-color locus, providing an alternative promoter that is variably DNA methylated in genetically identical individuals. This results in variable expressivity of coat color that is inherited transgenerationally. Here, a systematic genome-wide screen identifies multiple C57BL/6J murine IAPs with Avy epigenetic properties. Each exhibits a stable methylation state within an individual but varies between individuals. Only in rare instances do they act as promoters controlling adjacent gene expression. Their methylation state is locus-specific within an individual, and their flanking regions are enriched for CTCF. Variably methylated IAPs are reprogrammed after fertilization and re-established as variable loci in the next generation, indicating reconstruction of metastable epigenetic states and challenging the generalizability of non-genetic inheritance at these regions.
Animals, Mice, Inbred C57BL, Mice, Genomic Instability, Retroelements, DNA Methylation, Transcription, Genetic, Epigenesis, Genetic, Heredity, Binding Sites, Genes, Intracisternal A-Particle, Protein Binding, Genome, Male, Agouti Signaling Protein, Genetic Loci, CCCTC-Binding Factor
Medical Research Council (MR/J001597/1)
Wellcome Trust (086838/Z/08/Z)
Wellcome Trust (095606/Z/11/Z)
External DOI: https://doi.org/10.1016/j.cell.2018.09.043
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285629
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/