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1.
Cell ; 175(5): 1259-1271.e13, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30454646

RESUMO

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.


Assuntos
Metilação de DNA , Epigênese Genética , Genes de Partícula A Intracisternal , Instabilidade Genômica , Proteína Agouti Sinalizadora/genética , Animais , Sítios de Ligação , Fator de Ligação a CCCTC/química , Fator de Ligação a CCCTC/metabolismo , Loci Gênicos , Genoma , Hereditariedade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Retroelementos , Transcrição Gênica
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