Transcriptomics

Dataset Information

297

M6A RNA Methylation is Critical for Adequate Exit from Naïve Pluripotency and Execution of Mammalian Development (3p-Seq)


ABSTRACT: In this study we identify Mettl3, an m6A RNA modification writer, as a critical regulator for terminating naïve pluripotency and a positive maintainer of primed pluripotency in vitro and in vivo. Remarkably, Mettl3 knockout pre-implantation epiblasts and naïve ES cells, entirely lack m6A on coding mRNAs and are viable. Yet, they fail to adequately terminate the naïve pluripotent state, and subsequently undergo aberrant priming and early lineage commitment at the post-implantation stage. A comprehensive functional and genomic analysis involving profiling of m6A, RNA transcription and translation in Mettl3 wild-type and knockout pluripotent and differentiated cells, identified m6A as a critical determinant that destabilizes secondary naïve specific pluripotency genes Esrrb, Klf4 and Nanog, and restrains their transcript stability and translation efficiency. In summary, our findings provide for the first time evidence for a critical role for an mRNA epigenetic modification in early mammalian development in vivo, and identify a mechanism that functionally regulates mouse naïve and primed pluripotency in an opposing manner. 3' polyA RNA-sequencing (equivalent to Digital Gene Expression) measured in mouse Embryonic Stem Cells (ESCs) and mouse Embriod bodies (EBs) 0,4 & 8 hours after treatment with Actinomycin which halts transcription. Measured in both WT and Mettl3-KO cells.

ORGANISM(S): Mus musculus  

SUBMITTER: Nitzan Kol   Gidi Rechavi  Sharon Moshitch-Moshkovitz  Jacob Hanna  Shay Geula  Noa Novershtern 

PROVIDER: E-GEOD-61994 | ArrayExpress | 2014-11-02

SECONDARY ACCESSION(S): GSE61994SRP048595PRJNA262905

REPOSITORIES: GEO, ArrayExpress, ENA

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