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Acetaminophen-induced acute liver injury abrogates the cytosine methylation pathway.

PURPOSE: Acetaminophen overdose is a leading cause of drug-induced liver injury (DILI) and acute liver failure. Traditional markers such as … suppression correlated with increased global 5-methylcytosine (5mC) levels, indicating enhanced DNA methylation. Importantly, these epigenetic changes occurred at early stages of acetaminophen exposure, preceding overt necrosis. CONCLUSION: This study demonstrates that miRNA-mediated downregulation of TET enzymes and the resulting accumulation of 5mC represe …

Изменчивость метилирования и транскрипция LINE-1 в множестве миеломы.

Множественная миелома (ММ) — вид гематологического рака, который возникает в результате неконтролируемого распространения плазменных клеток. Помимо частых генетических мутаций злокачественные плазменные клетки характеризуются изменениями эпигенома. Клетки миэломы демонстрируют общегеномную потерю метилирования ДНК и соответствующее увеличение "активных" хроматинов. Эпигенетическая реконструкция, которая происходит в раковых геномах, связана с потерей глушителя в транспозиционных элементах, что может повлиять на регулирование генома. С помощью парного эпигеномного и транскриптомного профилирова

Совпадение в аннотации оригинала
Multiple myeloma (MM) is a type of hematological cancer that arises from uncontrolled proliferation of plasma cells. In addition to frequent genetic mutations, malignant plasma cells are characterized by alterations to the epigenome. Myeloma cells display a genome-wide loss of DNA methylation and a corresponding increase in "active" chromatin modifications. …

DNA methylation and gene expression signatures for common childhood infections.

BACKGROUND: Early life exposure to common pathogens and a high pathogen burden during childhood can have long-term effects on immune development and overall health. These infections can trigger molecular changes, including alterations in gene expression and DNA methylation (DNAm), which regulate immune and metabolic pathways. Our aim was to identify biological processes underlying differential patterns of DNAm and gene expression in whole blood by infection status in European children. RESULTS: In the Rhea (Greece) and INMA (Spain) cohorts, serum/plasma samples collected at mean ages of 4 and…

Read-level DNA methylation deconvolution enhances circulating tumor DNA detection.

DNA methylation is a key epigenetic modification underlying cellular identity. Conventional methods based on CpG site-level data often lack sensitivity in detecting low-frequency methylation signals. Here, we present Alpha, a novel method combining unbiased segmentation with robust read-level identification of low frequency cell-type-specific methylation signals. Methylation markers identified by Alpha exhibited significant enrichment in regulatory genomic elements such as enhancers, active promoters, and transcription factor binding sites. In simulated cell-type admixtures, Alpha-derived mark…

Longitudinal Analysis of Placental IRS1 DNA Methylation and Childhood Obesity.

Accumulating evidence suggests that the predisposition to metabolic diseases is established in utero through epigenomic modifications. However, it remains unclear whether childhood obesity results from preexisting epigenomic alterations or whether obesity itself induces changes in the epigenome. This study aimed to identify DNA methylation marks in the placenta associated with obesity-related outcomes in children at age 6 and to assess these marks in blood samples at age 6 and whether they correlate with obesity-related outcomes at that time. Using an epigenome-wide DNA methylation microarray …

Decitabine-mediated DNA methylation dynamics at pericentromeric satellite 2 repeats.

The hypomethylating agents (HMAs) 5-azacytidine (vidaza-AZA) and 5-aza-2'-deoxycytidine (decitabine-DAC) are part of the standard of care for the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, the molecular events mediated by HMAs in MDS and AML are poorly understood, and the efficacy of MDS and AML treatments is still improvable. The majority of CpG dinucleotides are located at satellite repeats, and their methylation levels are known to play a fundamental role in ensuring the genomic stability of cells. HMAs are believed to act through a plethora of e…

DNA Methylation-Regulated ZDHHC13 Promotes the Progression of Parkinson's Disease.

Recent studies suggest that palmitoylation may influence proteins involved in neurotransmission and neurodegenerative changes, such as pathological α-synuclein. However, the role of palmitoylation in Parkinson's disease (PD) has not been systematically investigated. Additionally, findings on DNA methylation changes and PD-associated gene expression remain inconsistent. This study aims to explore the causal relationship and mechanisms between palmitoylation genes, DNA methylation, and PD using Mendelian Randomization (MR). This study employed two-sample MR analysis, summary-data-based Mendelian…

Arginine Methylation by PRMT1 Affects ADAMTS13 Secretion and Enzymatic Activity.

BACKGROUND: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, 13), primarily synthesized in hepatic stellate and endothelial cells, plays a pivotal role in regulation of hemostasis by proteolytic cleavage of von Willebrand factor. Severe deficiency of plasma ADAMTS13 activity may result in thrombotic thrombocytopenic purpura, a potentially fatal blood disorder. ADAMTS13 undergoes posttranslational modifications including glycosylation, citrullination, oxidation. The present study determines the impact of arginine methylation by PRMT1 (protein arginine methyltransf…

RNA methylation homeostasis in ocular diseases: All eyes on Me.

RNA methylation is a pivotal epigenetic modification that adjusts various aspects of RNA biology, including nuclear transport, stability, and the efficiency of translation for specific RNA candidates. The methylation of RNA involves the addition of methyl groups to specific bases and can occur at different sites, resulting in distinct forms, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanosine (m7G). Maintaining an optimal equilibrium of RNA methylation is crucial for fundamental cellular activities such as cell survival, proliferation, and …

AutoMethyc: an automated methylation analysis for massively parallel sequencing data.

MOTIVATION: Bisulfite sequencing (BS-Seq) enables a comprehensive and detailed analysis of DNA methylation patterns at single-nucleotide resolution. While methylation differences can contribute to various diseases, their sincronous occurrence at distinct loci complicates understanding. Therefore, advanced tools are essential to facilitate the identification and analysis of methylation programs and patterns. RESULTS: AutoMethyc provides a comparative approach by integrating different algorithms coordinated and optimized for use on desktop computers and servers. The workflow evaluates the methy…

DNA methylation landscapes in human cells and their chromatin determinants.

Acetaminophen (APAP) overdose is a clinically relevant model of drug hepatotoxicity and acute liver failure. After decades of research, many aspects of the mechanism of APAP-induced liver injury are well established. These include the cytochrome P450 2E1-mediated formation of a reactive metabolite, hepatic glutathione depletion, mitochondrial protein adduct formation with oxidant stress and peroxynitrite formation, iron-catalyzed protein nitration in mitochondria, the opening of the mitochondrial permeability transition pore, and release of mitochondrial intermembrane proteins including endonu

Diagnostic and prognostic value of polygene methylation detection in ascites.

OBJECTIVE: To explore a novel combination of methylation markers for the differential diagnosis of malignant ascites (MA). MATERIALS AND METHODS: A cohort of 164 cancer patients and 20 patients with benign disease presenting with ascites was enrolled. Ascites was tested by means of cytopathological routine diagnosis and DNA methylation detection of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cytological specimens. DNA methylation in bisulfite-converted DNA was determined using semi-quantitative methylation-specific real-time PCR (MS-PCR). In addition, Kaplan-Meier method was used to plot the Ove…

DNA methylation biomarkers of intellectual/developmental disability across the lifespan.

Epigenetic mechanisms, including DNA methylation, act at the interface of genes and environment by allowing a static genome to respond and adapt to a dynamic environment during the lifespan of an individual. Genome-wide DNA methylation analyses on a wide range of human biospecimens are beginning to identify epigenetic biomarkers that can predict risk of intellectual/developmental disabilities (IDD). DNA methylation-based epigenetic signatures are becoming clinically useful in categorizing benign from pathogenic genetic variants following exome sequencing. While DNA methylation marks differ by …

The impact of YTHDF2-mediated NCOA4 methylation on myocardial ferroptosis.

The N6-Methyladenosine (m6A) modification is prevalent across various RNA species, including messenger RNAs (mRNAs) and long non-coding RNAs … elucidated that YTHDF2 suppresses the expression of nuclear receptor coactivator 4 (NCOA4) via m6A methylation. Furthermore, the inhibition of cardiomyocyte ferroptosis by YTHDF2 is contingent upon its regulation of NCOA4. Additionally, the enzyme methyltransferase-like 3 (METTL3) was identified as a pivotal factor in the m6A-mediated degradation of NCOA4 mR …

ID1 boosts antiviral immunity by countering PRMT5-mediated STING methylation.

The stimulator of interferon genes (STING) is a vital protein for the activation of the type I interferon signaling pathway. Despite its critical role in immune response, the regulatory role of methylation in STING activation remains unclear. This study demonstrated that the inhibitor of DNA binding 1 (ID1) enhanced STING-mediated gene expression during viral infection. Mechanistically, protein arginine methyltransferase 5 (PRMT5) interacts with STING and facilitates symmetric dimethylation at the Arg281 residue, thereby inhibiting STING activation. Conversely, methylation-defective STING muta…

MRI features of pleomorphic xanthoastrocytoma defined by DNA methylation profile.

INTRODUCTION: Pleomorphic xanthoastrocytomas (PXA) are primary brain tumors challenging to diagnose due to their morphological and molecular overlap with other tumors. While DNA methylation profiling (MP) aids pathological classification, it alone may be inconclusive. Magnetic resonance imaging (MRI), routinely performed for lesion assessment, provides valuable information. Combining histo-molecular features, MP, and MRI is thus beneficial, particularly in cases of diagnostic uncertainty. In this study, we retrospectively analyzed MRI features of methylation-confirmed PXAs (mcPXAs) versus tumo…

Histone H3 lysine 9 tri-methylation is associated with pterygium.

BACKGROUND: Pterygium, abnormal growths of conjunctival tissue onto the cornea, are common ocular surface conditions with a high risk of rec … profiles of patients with pterygium, focusing on histone H3 lysine 4 (H3K4) and lysine 9 (H3K9) trimethylation (me3). While H3K4me3 levels showed no significant genome-wide change, they were significantly altered in genes related to development and ocular diseases. Conversely, H3K9me3 levels were markedly elevated genome-wide, particularly at the promoters o …

DNA methylation modification: Dawn of research on cornea-related diseases.

DNA methylation is a significant form of epigenetic modification that plays a crucial role in the occurrence and progression of diseases by regulating gene expression. Recent advancements in our understanding of DNA methylation have demonstrated its involvement in corneal damage repair and various corneal diseases. This article reviews the mechanisms and effects of DNA methylation modifications in corneal injury repair, keratoconus, corneal dystrophy, keratitis, and other related conditions. The aim is to enhance our understanding of the vital role of DNA methylation in the pathogenesis of cor…

m6A mRNA methylation by METTL14 regulates early pancreatic cell differentiation.

N6-methyladenosine (m6A) is the most abundant chemical modification in mRNA and plays important roles in human and mouse embryonic stem cell pluripotency, maintenance, and differentiation. We have recently reported that m6A is involved in the postnatal control of β-cell function in physiological states and in type 1 and 2 diabetes. However, the precise mechanisms by which m6A acts to regulate the development of human and mouse pancreas are unexplored. Here, we show that the m6A landscape is dynamic during human pancreas development, and that METTL14, one of the m6A writer complex proteins, is

Placental methylation and pro-inflammatory protein levels in cord blood.

INTRODUCTION: The neonates' inflammatory response may in part be shaped during development by the placental epigenome, but evidence is scarce. We investigated the association between placental DNA methylation and pro-inflammatory proteins in cord blood. METHODS: A total of 249 mother-child dyads from the Harvard Epigenetic Birth Cohort were included in this study. Genome-wide methylation in placental DNA was assessed using the Illumina Human Methylation 450 Bead Chip array and verified by pyrosequencing. Cord blood inflammation markers assessed were interleukin-6, interleukin-8 and tumor necr…