DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus

Kaaij, L. T. J., van de Wetering, M., Fang, F., Decato, B., Molaro, A., van de Werken, H. J. G., van Es, J. H., Schuijers, J., de Wit, E., de Laat, W., Hannon, G. J., Clevers, H. C., Smith, A. D., Ketting, R. F. (2013) DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus. Genome Biology, 14 (5). ISSN 1465-6906

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URL: http://www.ncbi.nlm.nih.gov/pubmed/23714178
DOI: 10.1186/gb-2013-14-5-r50

Abstract

Background: DNA methylation is of pivotal importance during development. Previous genome-wide studies identified numerous differentially methylated regions upon differentiation of stem cells, many of them associated with transcriptional start sites. Results: We present the first genome-wide, single-base-resolution view into DNA methylation dynamics during differentiation of a mammalian epithelial stem cell: the mouse small intestinal Lgr5+ stem cell. Very little change was observed at transcriptional start sites and our data suggest that differentiation-related genes are already primed for expression in the stem cell. Genome-wide, only 50 differentially methylated regions were identified. Almost all of these loci represent enhancers driving gene expression in the differentiated part of the small intestine. Finally, we show that binding of the transcription factor Tcf4 correlates with hypo-methylation and demonstrate that Tcf4 is one of the factors contributing to formation of differentially methylated regions. Conclusions: Our results reveal limited DNA methylation dynamics during small intestine stem cell differentiation and an impact of transcription factor binding on shaping the DNA methylation landscape during differentiation of stem cells in vivo.

Item Type: Paper
Uncontrolled Keywords: Adult stem cells Differentiation DNA Methylation Methylome Enhancer Tcf4 de-novo methylation self-renewal transcription factor in-vitro lgr5 patterns genome dnmt3b methyltransferases pluripotent
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
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Matt Covey
Date Deposited: 11 Nov 2013 21:09
Last Modified: 07 Apr 2015 14:43
PMCID: PMC4053812
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28856

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