| First Author | Kazachenka A | Year | 2018 |
| Journal | Cell | Volume | 175 |
| Issue | 5 | Pages | 1259-1271.e13 |
| PubMed ID | 30454646 | Mgi Jnum | J:357022 |
| Mgi Id | MGI:6259265 | Doi | 10.1016/j.cell.2018.09.043 |
| Citation | Kazachenka A, et al. (2018) Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance. Cell 175(5):1259-1271.e13 |
| abstractText | 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. |
