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Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance

Kazachenka A, Bertozzi TM, Sjoberg-Herrera MK, Walker N, Gardner J, Gunning R, Pahita E, Adams S, Adams D, Ferguson-Smith AC (2018) Cell 2018 Oct; doi.org/10.1016/j.cell.2018.09.043 

Web URL: Read the abstract and full research on Cell.com here

Abstract:

Highlights

  • Repertoire of variably methylated repeat elements defined in inbred mice
  • VM-IAPs are flanked by CTCF binding sites, and very few act as promoters
  • Methylation variability is re-established from one generation to the next
  • Memory of parental methylation state is an exception rather than the rule

Summary

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 Avyepigenetic 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.

Graphical Abstract

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