Evidence map›Paper›PMID 23714178›Full record

ArticleGenome biology2013

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

Lucas T J Kaaij, Marc van de Wetering, Fang Fang, Benjamin Decato, Antoine Molaro, Harmen J G van de Werken, Johan H van Es, Jurian Schuijers, Elzo de Wit, Wouter de Laat and 4 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.

  1. Pooled it
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  7. Modeling DNA methyltransferase function to predict epigenetic correlation patterns in healthy and cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2025
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 3 countries.

Lucas T J Kaaij
Marc van de Wetering
Fang Fang
Benjamin Decato
Antoine Molaro
Harmen J G van de Werken
Johan H van Es
Jurian Schuijers
Elzo de Wit
Wouter de Laat
Gregory J Hannon
Hans C Clevers
Andrew D Smith
René F Ketting
Hubrecht Institute for Developmental Biology and Stem Cell Research · NLUniversity of Southern California · USCold Spring Harbor Laboratory · USHoward Hughes Medical Institute · USInstitute of Molecular Biology · DE

Funding

Analytic tools to examine high-resolution and genome-scale DNA methylation dataR01HG005238 · NHGRI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SMITH, ANDREW DAVID · 2010 to 2013
$1.5M
Howard Hughes Medical InstituteNHGRI NIH HHS R01 HG005238
6 · The paper itself

Abstract

backgroundDNA 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.

resultsWe 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.

conclusionsOur 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.

Indexed as

Cell DifferentiationAdult Stem CellsAnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsChromatinDNA MethylationGene Expression RegulationIntestine, SmallMiceMolecular Sequence DataReceptors, G-Protein-CoupledTranscription Factor 4Basic Helix-Loop-Helix Leucine Zipper Transcription FactorsChromatinLgr5 protein, mouseReceptors, G-Protein-CoupledTcf4 protein, mouseTranscription Factor 4

Identifiers

PMID23714178
PMCPMC4053812
OpenAlexW2145518488

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.