ArticlePloS one2009
Insulin gene expression is regulated by DNA methylation.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01663298 (FGF2 Promoter Hypermethylation and Implant Wound Healing Among Smokers and Diabetics), which is not on this map. Cited by 157 papers, 1 of them a synthesis that pooled 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.
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.
FGF2 Promoter Hypermethylation and Implant Wound Healing Among Smokers and Diabetics
Who cites it
157 citing papers in PubMed, 1 synthesis or guideline pooled it, 306 citations in OpenAlex.
- DNA methylation and type 2 diabetes: a systematic review.Clinical epigenetics · 2024Pooled it
- Immune therapy and β-cell death in type 1 diabetes.Diabetes · 2013Trial
- Hypermethylation at loci sensitive to the prenatal environment is associated with increased incidence of myocardial infarction.International journal of epidemiology · 2012Trial
- The role of epigenetic signatures in type 2 diabetes: therapeutic advances and lifestyle interventions.Acta diabetologica · 2026Review
- Systematic and proactive evaluation of AIRE missense variant effects.American journal of human genetics · 2026Article
- Narcolepsy is (not) an autoimmune disease.Nature reviews. Neurology · 2026Review
- DNMT3A/TET2-mediated epigenetic alteration in Type-1 diabetes dysregulates the haematopoiesis.Molecular biology reports · 2026Review
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- Polyadenylation of insulin mRNA by Tent5a regulates pancreatic beta cells.Nature communications · 2026Article
- TBL1X/TBL1XR1 govern β-cell identity through a PAX6-containing gene regulatory network.Nature communications · 2026Article
- i-Motif, not G-quadruplex, stability regulates insulin expression.Nucleic acids research · 2026Article
- MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.Frontiers in epigenetics and epigenomics · 2026Review
- The impact of obesity on bone health: molecular pathways, metabolic interactions, and associated pathologies.International journal of obesity (2005) · 2026Review
- TSC22D1 is a newly identified inhibitor of insulin secretion in pancreatic beta cells.The FEBS journal · 2025Article
- Systematic and proactive evaluation of AIRE missense variant effects.bioRxiv : the preprint server for biology · 2025Article
- Affinity-selected peptide ligands specifically bind i-motif DNA and modulate c-Myc gene expression.Nucleic acids research · 2025Article
- Bioinformatic Characterization of Genes That Are Correlated to the Progression of Breast Cancer to Breast Cancer Brain Metastasis.Cancer reports (Hoboken, N.J.) · 2025Article
- Comprehending the Epidemiology and Aetiology of Childhood Obesity: Integrating Life Course Approaches for Prevention and Intervention.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025Review
- Amplicon sequence proportion: A novel method for HRM primer design in DNA methylation analysis among marginalized rural population in Southern Mexico.Biology methods & protocols · 2025Article
- Exploring the key role of DNA methylation as an epigenetic modulator in oxidative stress related islet cell injury in patients with type 2 diabetes mellitus: a review.Journal of diabetes and metabolic disorders · 2024Review
97 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundInsulin is a critical component of metabolic control, and as such, insulin gene expression has been the focus of extensive study. DNA sequences that regulate transcription of the insulin gene and the majority of regulatory factors have already been identified. However, only recently have other components of insulin gene expression been investigated, and in this study we examine the role of DNA methylation in the regulation of mouse and human insulin gene expression. METHODOLOGY/PRINCIPAL
findingsGenomic DNA samples from several tissues were bisulfite-treated and sequenced which revealed that cytosine-guanosine dinucleotide (CpG) sites in both the mouse Ins2 and human INS promoters are uniquely demethylated in insulin-producing pancreatic beta cells. Methylation of these CpG sites suppressed insulin promoter-driven reporter gene activity by almost 90% and specific methylation of the CpG site in the cAMP responsive element (CRE) in the promoter alone suppressed insulin promoter activity by 50%. Methylation did not directly inhibit factor binding to the CRE in vitro, but inhibited ATF2 and CREB binding in vivo and conversely increased the binding of methyl CpG binding protein 2 (MeCP2). Examination of the Ins2 gene in mouse embryonic stem cell cultures revealed that it is fully methylated and becomes demethylated as the cells differentiate into insulin-expressing cells in vitro. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that insulin promoter CpG demethylation may play a crucial role in beta cell maturation and tissue-specific insulin gene expression.
Indexed as
Identifiers
What OpenQuestion holds
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.