ArticlePLoS genetics2013
DNA methylation restricts lineage-specific functions of transcription factor Gata4 during embryonic stem cell differentiation.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 47 citations in OpenAlex.
- The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine.Regenerative therapy · 2025Review
- ETV2/ER71 regulates hematovascular lineage generation and vascularization through an H3K9 demethylase, KDM4A.iScience · 2025Article
- Epigenetic reshaping through damage: promoting cell fate transition by BrdU and IdU incorporation.Cell & bioscience · 2024Article
- REV7: a small but mighty regulator of genome maintenance and cancer development.Frontiers in oncology · 2024Review
- Mesp1 controls the chromatin and enhancer landscapes essential for spatiotemporal patterning of early cardiovascular progenitors.Nature cell biology · 2022Article
- DNMT1 regulates the timing of DNA methylation by DNMT3 in an enzymatic activity-dependent manner in mouse embryonic stem cells.PloS one · 2022Article
- Deacetylase-independent function of SIRT6 couples GATA4 transcription factor and epigenetic activation against cardiomyocyte apoptosis.Nucleic acids research · 2020Article
- All roads lead to Rome: the many ways to pluripotency.Journal of assisted reproduction and genetics · 2020Review
- New tools for cell reprogramming and conversion: Possible applications to livestock.Animal reproduction · 2019Article
- Context-Specific Transcription Factor Functions Regulate Epigenomic and Transcriptional Dynamics during Cardiac Reprogramming.Cell stem cell · 2019Article
- Derivation of hypermethylated pluripotent embryonic stem cells with high potency.Cell research · 2018Article
- SCODE: an efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation.Bioinformatics (Oxford, England) · 2017Article
- Mechanisms of pluripotency maintenance in mouse embryonic stem cells.Cellular and molecular life sciences : CMLS · 2017Review
- Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.PLoS genetics · 2015Article
- BMP4 depletion by miR-200 inhibits tumorigenesis and metastasis of lung adenocarcinoma cells.Molecular cancer · 2015Article
- Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence.The EMBO journal · 2015Article
- Comparison of reprogramming genes in induced pluripotent stem cells and nuclear transfer cloned embryos.Stem cell reviews and reports · 2014Article
- The putative promoters of germ cell-specific genes and Nanog are hypomethylated in chicken sperm.The Journal of reproduction and development · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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. 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. Gata4-binding-site profiles and DNA methylation analyses suggested that DNA methylation modulates the Gata4 response through diverse mechanisms. 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.
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Registered trials
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.