Glycation DNA immunoprecipitation sequencing (GlyDIP-seq) for detecting epigenetic effects unique to diabetes [DIP-Seq]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE298780 | GEO | 2026/05/18
REPOSITORIES: GEO
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Project description:DNA glycation, a non-enzymatic modification triggered by reactive metabolites such as methylglyoxal (MG), has been implicated in various metabolic and neurological disorders. However, its genome-wide distribution and biological consequences in the developing brain remain largely unexplored. To address this gap, we developed a novel method, GlyDIP-seq, which enables high-resolution profiling of glycation-derived DNA lesions (specifically N²-carboxyethyl-2'-deoxyguanosine, CEdG) across the genome.
2026-05-18 | GSE296615 | GEO
Project description:DNA glycation, a non-enzymatic modification triggered by reactive metabolites such as methylglyoxal (MG), has been implicated in various metabolic and neurological disorders. However, its genome-wide distribution and biological consequences in the developing brain remain largely unexplored. To address this gap, we developed a novel method, GlyDIP-seq, which enables high-resolution profiling of glycation-derived DNA lesions (specifically N²-carboxyethyl-2'-deoxyguanosine, CEdG) across the genome.
2026-05-18 | GSE303270 | GEO
Project description:Diabetic kidney disease (DKD) is a leading cause of death in patients with diabetes. An early precursor to DKD is endothelial cell dysfunction (ECD), a factor that often precedes and exacerbates vascular disease progression. We previously discovered that covalent adducts formed on DNA, RNA, and proteins by reactive metabolic by-product methylglyoxal (MG) predict DKD risk in patients with type 1 diabetes up to 16 years pre-diagnosis. However, the mechanisms by which MG-adducts contribute to vascular disease onset and progression remain unclear. Here, we report that the most predominant MG-induced nucleoside adducts, N2-(1-carboxyethyl)-deoxyguanosine (CEdG) and N2-(1-carboxyethyl)-guanosine (CEG), drive endothelial dysfunction. Following CEdG or CEG exposure, primary human umbilical vein endothelial cells (HUVECs) undergo endothelial dysfunction, resulting in enhanced monocyte adhesion, increased reactive oxygen species production, endothelial permeability, impaired endothelial homeostasis, and exhibit a dysfunctional transcriptomic signature. These effects were discovered to be mediated through the receptor for advanced glycation end products (RAGE), as an inhibitor for intracellular RAGE signaling diminished these dysfunctional phenotypes. Therefore, we find that not only are MG-adducts biomarkers for DKD, this study reveals they may also have a dual role as potential drivers of vascular disease onset and progression and a new therapeutic modality.
2024-01-19 | GSE251645 | GEO
Project description:Cancer cells undergo profound metabolic reprogramming that elevates the intracellular levels of reactive byproducts such as methylglyoxal (MGO), which can non-enzymatically modify macromolecules in a process known as glycation. Histones are particularly susceptible to glycation, resulting in substantial alterations to chromatin structure and the epigenetic landscape. However, the mechanism by which histone glycation alters epigenetic landscape and impacts specific transcriptional output in vivo has remained unclear due to the lack of high-resolution tools. Here, we utilize adduct-, site-, and target-specific antibodies we developed against histone H3 glycation at arginine 17 (H3R17MG-H1), one of the most abundant histone glycation marks, to perform precise detection and enrichment of this mark. With these, we show that H3 glycation preferentially accumulates in euchromatin and directly crosstalks with a key active transcription-associated mark, H3K4me3, at transcription start sites. Mechanistically, H3 glycation antagonizes global H3K4me3 through dual pathways: by preventing the recruitment of WDR5-containing methyltransferase complexes to glycated H3 and by transcriptionally inducing KDM5 demethylases expression. The combined effects lead to genome-wide depletion of H3K4me3 and reprogramming of cellular transcriptional networks. Our findings reveal a distinct role for histone glycation as a potent modulator of epigenetic landscape and transcriptional output, serving as a direct link between altered metabolism and cell fate.
2026-03-07 | GSE317232 | GEO
Project description:Cancer cells undergo profound metabolic reprogramming that elevates the intracellular levels of reactive byproducts such as methylglyoxal (MGO), which can non-enzymatically modify macromolecules in a process known as glycation. Histones are particularly susceptible to glycation, resulting in substantial alterations to chromatin structure and the epigenetic landscape. However, the mechanism by which histone glycation alters epigenetic landscape and impacts specific transcriptional output in vivo has remained unclear due to the lack of high-resolution tools. Here, we utilize adduct-, site-, and target-specific antibodies we developed against histone H3 glycation at arginine 17 (H3R17MG-H1), one of the most abundant histone glycation marks, to perform precise detection and enrichment of this mark. With these, we show that H3 glycation preferentially accumulates in euchromatin and directly crosstalks with a key active transcription-associated mark, H3K4me3, at transcription start sites. Mechanistically, H3 glycation antagonizes global H3K4me3 through dual pathways: by preventing the recruitment of WDR5-containing methyltransferase complexes to glycated H3 and by transcriptionally inducing KDM5 demethylases expression. The combined effects lead to genome-wide depletion of H3K4me3 and reprogramming of cellular transcriptional networks. Our findings reveal a distinct role for histone glycation as a potent modulator of epigenetic landscape and transcriptional output, serving as a direct link between altered metabolism and cell fate.
2026-03-07 | GSE317229 | GEO
Project description:Cancer cells undergo profound metabolic reprogramming that elevates the intracellular levels of reactive byproducts. These include methylglyoxal (MGO), which can non-enzymatically modify macromolecules in a process known as glycation. Histones are particularly susceptible to glycation, resulting in substantial alterations to chromatin structure and the epigenetic landscape. However, the mechanism by which this impacts specific transcriptional outputs has been difficult to interrogate due to the lack of high-resolution tools. Here, we utilize adduct-, site-, and target-specific antibodies we developed against glycated histone H3 arginine 17 (H3R17MG-H1), one of the most abundant histone glycation marks, to determine its chromatin localization. We show that H3R17MG-H1 preferentially accumulates in euchromatin and directly crosstalks with H3K4me3, a key positive mark of activity at transcription start sites. Mechanistically, H3R17MG-H1 antagonizes global H3K4me3 through dual pathways: by preventing the local recruitment of WDR5-containing methyltransferases and by transcriptionally inducing KDM5 demethylases. The combined effects lead to a genome-wide depletion of H3K4me3 and reprogramming of cellular transcriptional networks. Overall, our findings reveal a distinct role for histone glycation as a potent modulator of the epigenetic landscape and transcriptional outputs, serving as a direct link between altered metabolism and epigenetic state.
2026-03-07 | GSE318078 | GEO
Project description:Non-enzymatic reactions in glycolysis lead to the accumulation of methylglyoxal (MGO), a reactive precursor to advanced glycation end-products (AGEs), which has been hypothesized to drive obesity and aging-associated pathologies. A combination of nicotinamide, lipoic acid, thiamine, pyridoxamine, and piperine (Gly-Low), was identified to lower glycation by reducing MGO and MGO-derived AGE, MG-H1, in mice. Administration of Gly-Low reduced food consumption, lowered body weight, improved insulin sensitivity, and increased survival in both leptin receptor-deficient (Leprdb) and wild-type C57B6/J mice. Unlike caloric restriction, Gly-Low modulated hypothalamic signaling by upregulating mTOR pathway signaling to inhibit ghrelin-mediated hunger response. Gly-Low also slowed hypothalamic aging and increased survival when administered as a late-life intervention, suggesting its potential benefits in ameliorating age-associated decline by inducing voluntary caloric restriction and reducing glycation.
2025-02-28 | GSE234483 | GEO
Project description:Methylglyoxal (MG) is a toxic byproduct of the glycolytic pathway and is quantitatively the most important precursor to advanced glycation end-products (AGEs). Insight into which proteins and in particular their individual modification sites are central to understand the involvement of MG and AGE in diabetes and aging related diseases. Here, we present a method to simultaneously monitor protein AGE formation in biological samples by employing an alkyne-labeled methylglyoxal probe. We apply the method to blood and plasma to demonstrate the impact of blood cell glyoxalase activity on plasma protein AGE formation. We move on to isolate proteins modified by the MG probe and accordingly can present the first general inventory of more than 100 proteins and 300 binding sites of the methylglyoxal probe on plasma as well as erythrocytic proteins.
2019-07-31 | PXD011314 | Pride
Project description:Alpha-synuclein (aSyn) is a central player in the pathogenesis of synucleinopathies due to its accumulation in typical protein aggregates in the brain. However, it is still unclear how it contributes to neurodegeneration. Type-2 diabetes mellitus is a risk factor for Parkinson’s disease (PD) and, interestingly, a common molecular alteration among these disorders is the age-associated increase in protein glycation. We hypothesized that glycation-induced neuronal dysfunction might be a contributing factor in synucleinopathies. Here, we dissected the specific impact of methylglyoxal (MGO, a glycating agent) in mice overexpressing aSyn in the brain. We found that MGO-glycation potentiates motor, cognitive, olfactory, and colonic dysfunction in aSyn transgenic (Thy1-aSyn) mice that received a single dose of MGO via intracerebroventricular (ICV) injection. aSyn accumulates in the midbrain, striatum, and prefrontal cortex, and protein glycation is increased in the cerebellum and midbrain. SWATH mass spectrometry analysis, used to quantify changes in the brain proteome, revealed that MGO mainly increase glutamatergic-associated proteins in the midbrain (NMDA, AMPA, glutaminase, VGLUT and EAAT1), but not in the prefrontal cortex, where it mainly affects the electron transport chain. Notably, the glycated proteins in the midbrain of Thy1-aSyn mice that received MGO strongly correlate with PD and dopaminergic pathways. Overall, we demonstrated that MGO-induced glycation accelerates PD-like sensorimotor and cognitive alterations and suggest that the increase of glutamatergic signaling may underly these events. Our study sheds new light into the enhanced vulnerability of the midbrain in PD-related synaptic dysfunction and suggests that glycation suppressors and anti-glutamatergic drugs may hold promise as disease-modifying therapies for synucleinopathies.
2022-05-20 | PXD032832 | Pride
Project description:Glycation is a covalent protein modification that accumulates in the cellular environment. Histone proteins are particularly susceptible to glycation due to their extremely long half-lives and nucleophilic disordered tails. Here, we performed ATAC-seq on 293T cells cultured in the presence or absence of 0.5mM methylglioxal, a reactive glycolytic intermediate, for 12 hours. We demonstrate that methylglioxal treatment is associated with changes in histone occupancy and chromatin architecture globally.
2019-02-14 | GSE121252 | GEO