Cortese, R;
Lewin, J;
Backdahl, L;
Krispin, M;
Wasserkort, R;
Eckhardt, F;
Beck, S;
(2011)
Genome-Wide Screen for Differential DNA Methylation Associated with Neural Cell Differentiation in Mouse.
PLOS ONE
, 6
(10)
, Article e26002. 10.1371/journal.pone.0026002.
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Abstract
Cellular differentiation involves widespread epigenetic reprogramming, including modulation of DNA methylation patterns. Using Differential Methylation Hybridization (DMH) in combination with a custom DMH array containing 51,243 features covering more than 16,000 murine genes, we carried out a genome-wide screen for cell- and tissue-specific differentially methylated regions (tDMRs) in undifferentiated embryonic stem cells (ESCs), in in-vitro induced neural stem cells (NSCs) and 8 differentiated embryonic and adult tissues. Unsupervised clustering of the generated data showed distinct cell- and tissue-specific DNA methylation profiles, revealing 202 significant tDMRs (p<0.005) between ESCs and NSCs and a further 380 tDMRs (p<0.05) between NSCs/ESCs and embryonic brain tissue. We validated these tDMRs using direct bisulfite sequencing (DBS) and methylated DNA immunoprecipitation on chip (MeDIP-chip). Gene ontology (GO) analysis of the genes associated with these tDMRs showed significant (absolute Z score>1.96) enrichment for genes involved in neural differentiation, including, for example, Jag1 and Tcf4. Our results provide robust evidence for the relevance of DNA methylation in early neural development and identify novel marker candidates for neural cell differentiation.
| Type: | Article |
|---|---|
| Title: | Genome-Wide Screen for Differential DNA Methylation Associated with Neural Cell Differentiation in Mouse |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0026002 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0026002 |
| Language: | English |
| Additional information: | © 2011 Cortese et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was partially supported by the European Union-sponsored project, High-throughput Epigenetic Regulatory Organisation in Chromatin (HEROIC), contract number 018883. LS was supported by a HEROIC grant, LSHG-CT-2005-018883, from the European Union under the Sixth Framework Programme to SB. SB was supported by the Wellcome Trust (084071) and a Royal Society Wolfson Research Merit Award. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.No additional external funding received for this study. |
| Keywords: | EMBRYONIC STEM-CELLS, EPIGENETIC CONTROL, GENE-EXPRESSION, PLURIPOTENT, MICROARRAY, METHYLOME, PROFILE, PCR |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1329785 |
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