biostudies-literatureKazachenka ACancer Research UKMedical Research CouncilWellcome TrustBiotechnology and Biological Sciences Research Council1259-1271.e13https://www.ebi.ac.uk/biostudies/studies/S-EPMC6242299biostudies-literatureUnknown175(5)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.CellIdentification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance.PMC6242299MR/L007428/1WT095606RR2171714356MR/J001597/1Bertozzi TMSjoberg-Herrera MKGunning RPahita EAdams SKazachenka AWalker NAdams DGardner JFerguson-Smith ACfalseIdentification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance.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.2018-01-01T00:00:00Z2018 Nov2021-02-20T05:33:40Z2019-03-27T00:08:46ZS-EPMC62422993045464610.1016/j.cell.2018.09.043