Andrews, Simon

Arand, Julia

Branco, Miguel R.

Cook, Simon J.

Dean, Wendy

Ficz, Gabriella

Hore, Timothy A.

Krueger, Felix

Lee, Heather J.

Oxley, David

Paul, Yu-Lee

Reik, Wolf

Santos, Fatima

Walter, Jörn

Clinical Epigenetics

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MEETING ABSTRACT Open AccessFGF signalling inhibition in ESCs drives rapidgenome-wide demethylation to the epigeneticground state of pluripotencyGabriella Ficz1, Timothy A Hore1, Fatima Santos1, Heather J Lee1, Wendy Dean1, Julia Arand2, Felix Krueger3,David Oxley4, Yu-Lee Paul1, Jörn Walter2, Simon J Cook5, Simon Andrews3, Miguel R Branco1,6, Wolf Reik1,6,7*From Birminghm Cancer Epigenetics Conference; Translational OpportunitiesBirmingham, UK. 16 May 2013Genome-wide erasure of DNA methylation takes placein primordial germ cells (PGCs) and early embryos andis linked with pluripotency. Inhibition of Erk1/2 andGsk3b signalling in mouse embryonic stem cells (ESCs)by small molecule inhibitors (called 2i) has recentlybeen shown to induce hypomethylation. We show bywhole-genome bisulphite sequencing that 2i induces rapidand genome-wide demethylation on a scale and patternsimilar to that in migratory PGCs and early embryos.Major satellites, intracisternal A particles (IAPs) andimprinted genes remain relatively resistant to erasure.Demethylation involves oxidation of 5-methylcytosine(5mC) to 5-hydroxymethylcytosine (5hmC), impairedmaintenance of 5mC and 5hmC and repression of thede novo methyltransferases (Dnmt3a, Dnmt3b) andDnmt3L. We identify a Prdm14 and Nanog binding cis-acting regulatory region in Dnmt3b that is highly respon-sive to signalling. These insights provide a novel frameworkfor understanding how signalling pathways regulate repro-gramming to an epigenetic ground state of pluripotency.Authors’ details1Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK.2Department of Biological Sciences, Institute of Genetics/Epigenetics,University of Saarland, Saarbrüken, Germany. 3Bioinformatics Group,Babraham Institute, Cambridge CB22 3AT, UK. 4Proteomics Research Group,Babraham Institute, Cambridge CB22 3AT, UK. 5Signalling Programme,The Babraham Institute, Cambridge, CB22 3AT, UK. 6Centre for TrophoblastResearch, University of Cambridge, Cambridge CB2 3EG, UK. 7Wellcome TrustSanger Institute, Hinxton CB10 1SA, UK.Published: 19 August 2013doi:10.1186/1868-7083-5-S1-S2Cite this article as: Ficz et al.: FGF signalling inhibition in ESCs drivesrapid genome-wide demethylation to the epigenetic ground state ofpluripotency. Clinical Epigenetics 2013 5(Suppl 1):S2.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submit* Correspondence: wolf.reik@babraham.ac.uk1Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UKFull list of author information is available at the end of the articleFicz et al. Clinical Epigenetics 2013, 5(Suppl 1):S2http://www.clinicalepigeneticsjournal.com/content/5/S1/S2© 2013 Ficz et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

FGF signalling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency

https://publikationen.sulb.uni-saarland.de/bitstream/20.500.11880/34465/1/1868-7083-5-S1-S2.pdf

FGF signalling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency

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