RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2014 
FD August 01 
VO 24 
IS 8 
SP 1251 
OP 1259 
DO 10.1101/gr.172809.114 
UL http://genome.cshlp.org/content/24/8/1251.abstract 
AB 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.