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Loss of transcriptional control over endogenous retroelements during reprogramming to pluripotency

Publié dansGenome research, vol. 24, no. 8, p. 1251-1259
Date de publication2014
Résumé

Endogenous retroelements (EREs) account for about half of the mouse or human genome, and their potential as insertional mutagens and transcriptional perturbators is suppressed by early embryonic epigenetic silencing. Here, we asked how ERE control is maintained during the generation of induced pluripotent stem cells (iPSCs), as this procedure involves profound epigenetic remodeling. We found that all EREs tested were markedly up-regulated during the reprogramming of either mouse embryonic fibroblasts, human CD34(+) cells, or human primary hepatocytes. At the iPSC stage, EREs of some classes were repressed, whereas others remained highly expressed, yielding a pattern somewhat reminiscent of that recorded in embryonic stem cells. However, variability persisted between individual iPSC clones in the control of specific ERE integrants. Both during reprogramming and in iPS cells, the up-regulation of specific EREs significantly impacted on the transcription of nearby cellular genes. While transcription triggered by specific ERE integrants at highly precise developmental stages may be an essential step toward obtaining pluripotent cells, the broad and unspecific unleashing of the repetitive genome observed here may contribute to the inefficiency of the reprogramming process and to the phenotypic heterogeneity of iPSCs.

Mots-clés
  • Retroelements
  • Reprogramming
  • IPSC
Citation (format ISO)
FRIEDLI, Marc et al. Loss of transcriptional control over endogenous retroelements during reprogramming to pluripotency. In: Genome research, 2014, vol. 24, n° 8, p. 1251–1259. doi: 10.1101/gr.172809.114
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Article (Published version)
accessLevelPublic
Identifiants
ISSN du journal1088-9051
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Informations techniques

Création12.08.2014 19:53:00
Première validation12.08.2014 19:53:00
Heure de mise à jour14.03.2023 21:48:23
Changement de statut14.03.2023 21:48:22
Dernière indexation16.01.2024 11:58:11
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