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Series GSE42923 Query DataSets for GSE42923
Status Public on Jun 27, 2013
Title FGF Signaling Inhibition in ESCs Drives Rapid Genome-wide Demethylation to the Epigenetic Ground State of Pluripotency
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Genome-wide erasure of DNA methylation takes place in primordial germ cells (PGCs) and early embryos but the signalling mechanisms that induce reprogramming are unknown. Here we show that inhibition of Erk1/2 and Gsk3b signalling in mouse embryonic stem cells (ESCs) by small molecule inhibitors (PD0325901 and CHIR99021, hereafter called 2i) induces genome-wide demethylation on a scale similar to that in PGCs and early embryos, with only major satellites, intracisternal A particles (IAPs) and imprinted genes relatively resistant to erasure. Demethylation involves oxidation of 5-methylcytosine (5mC) in part by Tet1 together with repression of the de novo methyltransferases (Dnmt3a, Dnmt3b) and their regulator Dnmt3L and we identify a cis-acting regulatory region in Dnmt3b that is highly responsive to signalling. Notably, this epigenetic and transcriptional ground state of pluripotency resembles closely that of inner cell mass (ICM) cells of the blastocyst. These insights provide a novel framework for understanding how signalling pathways regulate epigenetic reprogramming.
Overall design mRNA and methylation profiles of ES cells passaged with or without 2i inhibitors were generated by deep sequencing, using Illumina GAIIx and HiSeq.
Contributor(s) Ficz G, Hore TA, Santos F, Dean W, Krueger F, Oxley D, Cook SJ, Andrews SR, Branco M, Reik W
Citation(s) 23850245
Submission date Dec 14, 2012
Last update date May 15, 2019
Contact name Felix Krueger
Organization name Altos Labs
Department Bioinformatics
Street address Granta Park
City Cambridge
ZIP/Postal code CB21 6GP
Country United Kingdom
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL15103 Illumina HiSeq 1000 (Mus musculus)
Samples (12)
GSM1053451 P0 RNA-Seq
GSM1053452 Serum P12 (1) RNA-Seq
GSM1053453 Serum P12 (2) RNA-Seq
BioProject PRJNA183886
SRA SRP017572

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE42923_RAW.tar 5.3 Gb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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