ArticleClinical epigenetics2021
Increased PARylation impacts the DNA methylation process in type 2 diabetes mellitus.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- DNA methylation and type 2 diabetes: a systematic review.Clinical epigenetics · 2024Pooled it
- Associations of Accelerated DNA Methylation Aging Algorithms with Chronic Liver Disease and All-Cause Mortality.Biomedicines · 2026Article
- DNA Methylation-Guided Prediction and Validation of TAAD Molecular Targets.Biochemical genetics · 2026Article
- Approaches to repurposing reverse transcriptase antivirals in cancer.British journal of clinical pharmacology · 2025Review
- Immunoinflammation and post-translational modifications in the aging process.Journal of translational medicine · 2025Review
- Comprehensive dataset of interactors for the entire PARP family using TurboID proximity labeling.Scientific data · 2025Article
- Association Between Active DNA Demethylation and Liver Fibrosis in Individuals with Metabolic-Associated Steatotic Liver Disease (MASLD).International journal of molecular sciences · 2025Article
- Polyphenols, aging, and health: What can we expect from the food industry in the technology era?Frontiers in medicine · 2025Review
- Literary Identification of Differentially Hydroxymethylated DNA Regions for Type 2 Diabetes Mellitus: A Scoping Minireview.International journal of environmental research and public health · 2024Article
- Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma.Acta pharmacologica Sinica · 2023Article
- Updates on Triple-Negative Breast Cancer in Type 2 Diabetes Mellitus Patients: From Risk Factors to Diagnosis, Biomarkers and Therapy.Diagnostics (Basel, Switzerland) · 2023Review
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Review
- TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation.Epigenetics & chromatin · 2022Article
- Genome-wide Analysis Reflects Novel 5-Hydroxymethylcytosines Implicated in Diabetic Nephropathy and the Biomarker Potential.Extracellular vesicles and circulating nucleic acids · 2022Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundEpigenetic modifications, such as DNA methylation, can influence the genetic susceptibility to type 2 diabetes mellitus (T2DM) and the progression of the disease. Our previous studies demonstrated that the regulation of the DNA methylation pattern involves the poly(ADP-ribosyl)ation (PARylation) process, a post-translational modification of proteins catalysed by the poly(ADP-ribose) polymerase (PARP) enzymes. Experimental data showed that the hyperactivation of PARylation is associated with impaired glucose metabolism and the development of T2DM. Aims of this case-control study were to investigate the association between PARylation and global and site-specific DNA methylation in T2DM and to evaluate metabolic correlates.
resultsData were collected from 61 subjects affected by T2DM and 48 healthy individuals, recruited as controls. Global levels of poly(ADP-ribose) (PAR, a surrogate of PARP activity), cytosine methylation (5-methylcytosine, 5mC) and de-methylation intermediates 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) were determined in peripheral blood cells by ELISA-based methodologies. Site-specific DNA methylation profiling of SOCS3, SREBF1 and TXNIP candidate genes was performed by mass spectrometry-based bisulfite sequencing, methyl-sensitive endonucleases digestion and by DNA immuno-precipitation. T2DM subjects presented higher PAR levels than controls. In T2DM individuals, increased PAR levels were significantly associated with higher HbA1c levels and the accumulation of the de-methylation intermediates 5hmC and 5fC in the genome. In addition, T2DM patients with higher PAR levels showed reduced methylation with increased 5hmC and 5fC levels in specific SOCS3 sites, up-regulated SOCS3 expression compared to both T2DM subjects with low PAR levels and controls.
conclusionsThis study demonstrates the activation of PARylation processes in patients with T2DM, particularly in those with poor glycaemic control. PARylation is linked to dysregulation of DNA methylation pattern via activation of the DNA de-methylation cascade and may be at the basis of the differential gene expression observed in presence of diabetes.
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