RT Journal Article
SR Electronic
T1 A lncRNA/Lin28/<em>Mirlet7</em> axis coupled to DNA methylation fine tunes the dynamics of a cell state transition
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 131110
DO 10.1101/131110
A1 Meng Amy Li
A1 Paulo P. Amaral
A1 Priscilla Cheung
A1 Jan H. Bergmann
A1 Masaki Kinoshita
A1 Tüzer Kalkan
A1 Meryem Ralser
A1 Sam Robson
A1 Ferdinand von Meyenn
A1 Maike Paramor
A1 Fengtang Yang
A1 Caifu Chen
A1 Jennifer Nichols
A1 David L. Spector
A1 Tony Kouzarides
A1 Lin He
A1 Austin Smith
YR 2017
UL http://biorxiv.org/content/early/2017/04/26/131110.abstract
AB Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a condition poised for lineage specification. This process is controlled at transcriptional, post-transcriptional and epigenetic levels and non-coding RNAs are contributors to this regulation complexity. Here we identify a molecular cascade initiated by a long non-coding RNA (lncRNA), Ephemeron (Epn), that modulates the dynamics of exit from naïve pluripotency. Epn deletion delays the extinction of ESC identity, an effect mediated by perduring expression of the pivotal transcription factor Nanog. In the absence of Epn, Lin28a expression is reduced, resulting in an elevated level of Mirlet7g that suppresses de novo methyltransferases Dnmt3a/b. Dnmt3a/b deletion also retards exit from the ESC state, and is associated with delayed promoter methylation and slower down-regulation of Nanog. Altogether, our findings reveal a lncRNA/miRNA/DNA methylation axis that facilitates a timely stem cell state transition.