ArticleeLife2017
cAMP signaling regulates DNA hydroxymethylation by augmenting the intracellular labile ferrous iron pool.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Abnormal iron homeostasis mediates cochlear hair cell impairment and hearing loss in Gprasp2-deficient mice.Communications biology · 2026Article
- DHODH links mitochondrial bioenergetics, one-carbon metabolism, and DNA repair to sustain aggressive prostate adenocarcinoma.Cell communication and signaling : CCS · 2026Article
- TAM receptors mediate the Fpr2-driven pain resolution and fibrinolysis after nerve injury.Acta neuropathologica · 2024Article
- Sox10 Activity and the Timing of Schwann Cell Differentiation Are Controlled by a Tle4-Dependent Negative Feedback Loop.International journal of molecular sciences · 2024Article
- Small-Molecule Fluorescent Probes for Binding- and Activity-Based Sensing of Redox-Active Biological Metals.Chemical reviews · 2024Review
- Sleep and memory: The impact of sleep deprivation on transcription, translational control, and protein synthesis in the brain.Journal of neurochemistry · 2023Review
- Endogenous Glycoprotein GPM6a Is Involved in Neurite Outgrowth in Rat Dorsal Root Ganglion Neurons.Biomolecules · 2023Article
- Whole blood transcriptomic profiling identifies molecular pathways related to cardiovascular mortality in heart failure.European journal of heart failure · 2022Article
- Role of the Pbrm1 subunit and the PBAF complex in Schwann cell development.Scientific reports · 2022Article
- Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production.Science (New York, N.Y.) · 2022Article
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Ferroptosis Induction in Multiple Myeloma Cells Triggers DNA Methylation and Histone Modification Changes Associated with Cellular Senescence.International journal of molecular sciences · 2021Article
- Epigenomic regulation by labile iron.Free radical biology & medicine · 2021Article
- The epigenetic and morphogenetic effects of molecular oxygen and its derived reactive species in development.Free radical biology & medicine · 2021Article
- Vitamin C regulates Schwann cell myelination by promoting DNA demethylation of pro-myelinating genes.Journal of neurochemistry · 2021Article
- Emerging role of ferrous iron in bacterial growth and host-pathogen interaction: New tools for chemical (micro)biology and antibacterial therapy.Current opinion in chemical biology · 2021Review
- Ferrous Iron-Dependent Pharmacology.Trends in pharmacological sciences · 2021Review
- Activity-Based Sensing: A Synthetic Methods Approach for Selective Molecular Imaging and Beyond.Angewandte Chemie (International ed. in English) · 2020Review
- Dysregulation of 2-oxoglutarate-dependent dioxygenases by hyperglycaemia: does this link diabetes and vascular disease?Clinical epigenetics · 2020Review
- cAMP/EPAC Signaling Enables ETV2 to Induce Endothelial Cells with High Angiogenesis Potential.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
It is widely accepted that cAMP regulates gene transcription principally by activating the protein kinase A (PKA)-targeted transcription factors. Here, we show that cAMP enhances the generation of 5-hydroxymethylcytosine (5hmC) in multiple cell types. 5hmC is converted from 5-methylcytosine (5mC) by Tet methylcytosine dioxygenases, for which Fe(II) is an essential cofactor. The promotion of 5hmC was mediated by a prompt increase of the intracellular labile Fe(II) pool (LIP). cAMP enhanced the acidification of endosomes for Fe(II) release to the LIP likely through RapGEF2. The effect of cAMP on Fe(II) and 5hmC was confirmed by adenylate cyclase activators, phosphodiesterase inhibitors, and most notably by stimulation of G protein-coupled receptors (GPCR). The transcriptomic changes caused by cAMP occurred in concert with 5hmC elevation in differentially transcribed genes. Collectively, these data show a previously unrecognized regulation of gene transcription by GPCR-cAMP signaling through augmentation of the intracellular labile Fe(II) pool and DNA hydroxymethylation.
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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.