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Identification, 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 (A(vy)) locus, an endogenous retrovirus (ERV) of the intracisternal A particle (IAP) class retrotransposed upstream of the agouti coat-color locus, providing an alter...

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Detalles Bibliográficos
Autores principales: Kazachenka, Anastasiya, Bertozzi, Tessa M., Sjoberg-Herrera, Marcela K., Walker, Nic, Gardner, Joseph, Gunning, Richard, Pahita, Elena, Adams, Sarah, Adams, David, Ferguson-Smith, Anne C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242299/
https://www.ncbi.nlm.nih.gov/pubmed/30454646
http://dx.doi.org/10.1016/j.cell.2018.09.043
Descripción
Sumario:Generally repressed by epigenetic mechanisms, retrotransposons represent around 40% of the murine genome. At the Agouti viable yellow (A(vy)) 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 A(vy) 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.