ArticleThe Journal of biological chemistry2014
Paradoxical role of DNA methylation in activation of FoxA2 gene expression during endoderm development.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 120 citations in OpenAlex.
- A study on the correlation between DNA methylation and protein expression levels ofThe Journal of international medical research · 2026Article
- Epigenetic differences in non-plaque tissues of men with Peyronie's disease.The journal of sexual medicine · 2025Article
- Complementary Roles of DNA Methylation and miRNA in Regulating Gene Expression Under Environmental Stress in Biological Invasions.Evolutionary applications · 2025Article
- DNMT Enzymes and Their Impact on Cervical Cancer: A State-of-the-Art Review.International journal of molecular sciences · 2025Review
- Integrated study of DNA methylation and transcriptome: a new perspective for exploring the pathogenesis of Sjögren's syndrome.Epigenetics & chromatin · 2025Article
- Cell-context response to germ layer differentiation signals is predetermined by the epigenome in regionalized epiblast populations.Nature communications · 2025Article
- Human TSC2 mutant cells exhibit aberrations in early neurodevelopment accompanied by changes in the DNA Methylome.Human molecular genetics · 2025Article
- Dietary polyunsaturated fatty acids affect PPARγ promoter methylation status and regulate the PPARγ/COX2 pathway in some colorectal cancer cell lines.Genes & nutrition · 2025Article
- Analysis of the Transcriptional Control ofAnimals : an open access journal from MDPI · 2025Article
- Methylome-proteome integration after late-life voluntary exercise training reveals regulation and target information for improved skeletal muscle health.The Journal of physiology · 2025Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?Biomedicines · 2024Review
- Article
- DNA Methylation Dynamics in Response to Drought Stress in Crops.Plants (Basel, Switzerland) · 2024Review
- Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome.bioRxiv : the preprint server for biology · 2024Article
- Crosstalk within and beyond the Polycomb repressive system.The Journal of cell biology · 2024Review
- Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.Current issues in molecular biology · 2024Review
- Genome-Wide DNA Methylation Analysis and Functional Validation of Litter Size Traits in Jining Grey Goats.Genes · 2024Article
- Integrated molecular analysis reveals hypermethylation and overexpression of HOX genes to be poor prognosticators in isocitrate dehydrogenase mutant glioma.Neuro-oncology · 2023Article
- Comprehensive analysis of TLX2 in pan cancer as a prognostic and immunologic biomarker and validation in ovarian cancer.Scientific reports · 2023Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor FoxA2 is a master regulator of endoderm development and pancreatic beta cell gene expression. To elucidate the mechanisms underlying the activation of the FoxA2 gene during differentiation, we have compared the epigenetic status of undifferentiated human embryonic stem cells (hESCs), hESC-derived early endoderm stage cells (CXCR4+ cells), and pancreatic islet cells. Unexpectedly, a CpG island in the promoter region of the FoxA2 gene displayed paradoxically high levels of DNA methylation in expressing tissues (CXCR4+, islets) and low levels in nonexpressing tissues. This CpG island region was found to repress reporter gene expression and bind the Polycomb group protein SUZ12 and the DNA methyltransferase (DNMT)3b preferentially in undifferentiated hESCs as compared with CXCR4+ or islets cells. Consistent with this, activation of FoxA2 gene expression, but not CXCR4 or SOX17, was strongly inhibited by 5-aza-2'-deoxycytidine and by knockdown of DNMT3b. We hypothesize that in nonexpressing tissues, the lack of DNA methylation allows the binding of DNA methyltransferases and repressing proteins, such as Polycomb group proteins; upon differentiation, DNMT activation leads to CpG island methylation, causing loss of repressor protein binding. These results suggest a novel and unexpected role for DNA methylation in the activation of FoxA2 gene expression during differentiation.
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