A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation

Li, M. A., Amaral, P. P., Cheung, P., Bergmann, J. H., Kinoshita, M., Kalkan, T., Ralser, M., Robson, S., Meyenn, F. V., Paramor, M., Yang, F., Chen, C., Nichols, J., Spector, D. L., Kouzarides, T., He, L., Smith, A. (2017) A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation. Elife, 6. ISSN 2050-084x

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URL: https://www.ncbi.nlm.nih.gov/pubmed/28820723
DOI: 10.7554/eLife.23468

Abstract

Execution of pluripotency requires progression from the naive status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naive pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of Eprn, Lin28a expression is reduced which results in persistence of let-7 microRNAs, and the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. Dnmt3a/b deletion retards ES cell transition, correlating with delayed Nanog promoter methylation and phenocopying loss of Eprn or Lin28a. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of naive pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. Eprn illustrates how lncRNAs may introduce species-specific network modulations.

Item Type: Paper
Uncontrolled Keywords: Lin28a/Mirlet7 de novo DNA methylation developmental biology long non-coding RNA mouse pluripotency stem cell transition stem cells
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > long non-coding RNA
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > pluripotency
CSHL Authors:
Communities: CSHL labs > Spector lab
Depositing User: Matt Covey
Date Deposited: 23 Aug 2017 14:45
Last Modified: 03 Nov 2017 18:32
PMCID: PMC5562443
Related URLs:
URI: http://repository.cshl.edu/id/eprint/35253

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