TY - JOUR T1 - A lncRNA/Lin28/<em>Mirlet7</em> axis coupled to DNA methylation fine tunes the dynamics of a cell state transition JF - bioRxiv DO - 10.1101/131110 SP - 131110 AU - Meng Amy Li AU - Paulo P. Amaral AU - Priscilla Cheung AU - Jan H. Bergmann AU - Masaki Kinoshita AU - Tüzer Kalkan AU - Meryem Ralser AU - Sam Robson AU - Ferdinand von Meyenn AU - Maike Paramor AU - Fengtang Yang AU - Caifu Chen AU - Jennifer Nichols AU - David L. Spector AU - Tony Kouzarides AU - Lin He AU - Austin Smith Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/26/131110.abstract N2 - 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. ER -