title: DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus.
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.
authors.forename: Lucas T J
authors.initials: LT
authors.lastname: Kaaij
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Decato
authors.forename: Antoine
authors.initials: A
authors.lastname: Molaro
authors.forename: Harmen J G
authors.initials: HJ
authors.lastname: van de Werken
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Es
authors.forename: Jurian
authors.initials: J
authors.lastname: Schuijers
authors.forename: Elzo
authors.initials: E
authors.lastname: de Wit
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: Hans C
authors.initials: HC
authors.lastname: Clevers
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.forename: René F
authors.initials: RF
authors.lastname: Ketting
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D005786:Gene Expression Regulation; D007421:Intestine, Small / Q000166:cytology*; D051379:Mice; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000073940:Transcription Factor 4
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002843:Chromatin; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4