TY - JOUR A1 - Friedli, Marc A1 - Turelli, Priscilla A1 - Kapopoulou, Adamandia A1 - Rauwel, Benjamin A1 - Castro-Díaz, Nathaly A1 - Rowe, Helen M. A1 - Ecco, Gabriela A1 - Unzu, Carmen A1 - Planet, Evarist A1 - Lombardo, Angelo A1 - Mangeat, Bastien A1 - Wildhaber, Barbara E. A1 - Naldini, Luigi A1 - Trono, Didier T1 - Loss of transcriptional control over endogenous retroelements during reprogramming to pluripotency Y1 - 2014/08/01 JF - Genome Research JO - Genome Research SP - 1251 EP - 1259 DO - 10.1101/gr.172809.114 VL - 24 IS - 8 UR - http://genome.cshlp.org/content/24/8/1251.abstract N2 - 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. ER -