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Title: DNA Methylation Restricts Lineage-Specific Functions of Transcription Factor Gata4 during Embryonic Stem Cell Differentiation      
dateReleased:
06-24-2013
description:
DNA methylation changes dynamically during development and is essential for embryogenesis in mammals. However, how DNA methylation affects developmental gene expression and cell differentiation remains elusive. During embryogenesis, many key transcription factors are used repeatedly, triggering different outcomes depending on the cell type and developmental stage. Here, we report that DNA methylation modulates transcription-factor output in the context of cell differentiation. Using a drug-inducible Gata4 system and a mouse embryonic stem (ES) cell model of mesoderm differentiation, we examined the cellular response to Gata4 in ES and mesoderm cells. The activation of Gata4 in ES cells is known to drive their differentiation to endoderm. We show that the differentiation of wild-type ES cells into mesoderm blocks their Gata4-induced endoderm differentiation, while mesoderm cells derived from ES cells that are deficient in the DNA methyltransferases Dnmt3a and Dnmt3b can retain their response to Gata4, allowing lineage conversion from mesoderm cells to endoderm in part. Transcriptome analysis of the cells' response to Gata4 over time revealed groups of endoderm and mesoderm developmental genes whose expression was induced by Gata4 only when DNA methylation was lost, suggesting that DNA methylation restricts the ability of these genes to respond to Gata4, rather than controlling their transcription per se. Our data indicate that epigenetic regulation by DNA methylation functions as a heritable safeguard to prevent transcription factors from activating inappropriate downstream genes, thereby contributing to the restriction of the differentiation potential of somatic cells. To understand how mouse cells differentially respond to Gata4 in cell type- and DNA methylation-dependent manners and to examine what genes are differentially regulated, we analyzed temporal change of gene expression profile in response to Gata4 in ES or Flk1(+) mesoderm cells in WT and Dnmt3a-/-Dnmt3b-/- (DKO) background, in total 108 samples.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-36313
refinement:
raw
alternateIdentifiers:
36313
keywords:
functional genomics
dateModified:
06-02-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-GEOD-13912
name:
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-36313/E-GEOD-36313.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-36313/E-GEOD-36313.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36313
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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