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Stem Cell Reports ; 14(1): 60-74, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31902705

RESUMO

In mammals, LINE-1 (L1) retrotransposons constitute between 15% and 20% of the genome. Although only a few copies have retained the ability to retrotranspose, evidence in brain and differentiating pluripotent cells indicates that L1 retrotransposition occurs and creates mosaics in normal somatic tissues. The function of de novo insertions remains to be understood. The transdifferentiation of mouse embryonic fibroblasts to dopaminergic neuronal fate provides a suitable model for studying L1 dynamics in a defined genomic and unaltered epigenomic background. We found that L1 elements are specifically re-expressed and mobilized during the initial stages of reprogramming and that their insertions into specific acceptor loci coincides with higher chromatin accessibility and creation of new transcribed units. Those events accompany the maturation of neuronal committed cells. We conclude that L1 retrotransposition is a non-random process correlating with chromatin opening and lncRNA production that accompanies direct somatic cell reprogramming.


Assuntos
Transdiferenciação Celular/genética , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Elementos Nucleotídeos Longos e Dispersos , Animais , Biomarcadores , Técnicas de Cultura de Células , Linhagem Celular , Biologia Computacional/métodos , Imunofluorescência , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genoma , Camundongos , Retroelementos , Sequenciamento Completo do Genoma
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