5-hmC

BACKGROUND: Effective identification and development of new molecular methods for the diagnosis, treatment and prognosis of lung adenocarcinoma (LUAD) remains an urgent clinical need. DNA methylation patterns at cytosine bases in the genome are closely related to gene expression, and abnormal DNA methylation is frequently observed in various cancers. The ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) and promote locus-specific DNA methylation reversal. This study aimed to explore the role of the TET2 protein and its downstream effector, 5-hmC/5-mC DNA modification, in LUAD progression...

BACKGROUND: Primary cutaneous CD4+ small/medium-sized pleomorphic T-Cell lymphoproliferative disorder (PC-SMTLD) has been considered as a controversial dermatological disease that has been included in cutaneous T-cell lymphoma group, presenting most commonly as a solitary nodule and/or plaque with a specific and characteristic head and neck predilection. Due to the considerable overlap between PC-SMTLD and pseudolymphoma (PL), the differential diagnosis is often challenging. Methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas...

AIMS: Smoking causes DNA methylation (DNAm) alterations that lead to lung cancer development. Although the use of heated tobacco products (HTPs) has recently increased, their impact on health remains unclear. This study aimed to evaluate the effects of HTPs on DNAm and gene transcription in human lung epithelial cells in vitro. MAIN METHODS: Human lung adenocarcinoma (A549) cells with type II alveolar epithelial characteristics were treated with aerosol extracts of two HTPs or a smoke extract of combustible reference cigarette (RC)...

Introduction: The potentially unlimited number of cardiomyocyte (CMs) derived from human induced pluripotent stem cells (hiPSCs) in vitro facilitates high throughput applications like cell transplantation for myocardial repair, disease modelling, and cardiotoxicity testing during drug development. Despite promising progress in these areas, a major disadvantage that limits the use of hiPSC derived CMs (hiPSC-CMs) is their immaturity. Methods : Three hiPSC lines (PCBC-hiPSC, DP3-hiPSCs, and MLC2v-mEGFP hiPSC) were differentiated into CMs (PCBC-CMs, DP3-CMs, and MLC2v-CMs, respectively) with or without retinoic acid (RA)...

Obesity is a major health concern that is associated with altered gene transcription in the hypothalamus. However, the mechanisms controlling this gene expression dysregulation remain largely unknown. DNA 5-hydroxymethylation (5-hmC) is a potent transcriptional activator that is expressed at 10 times higher levels in the brain than the periphery. Despite this, no study has examined if DNA 5-hmC is altered in the brain following exposure to obesogenic diets or contributes to abnormal weight gain over time. Here, we used a rodent diet-induced obesity model in combination with quantitative molecular assays and CRISPR-dCas9 manipulations to test the role of hypothalamic DNA 5-hmC in abnormal weight gain in male and female rats...

β-glucosyltransferase (β-GT) can specifically catalyze the conversion of 5-hydroxymethylcytosine (5-hmC) to 5-glucosylhydroxy methylcytosine (5-ghmC), and it is associated with the control of phage-specific gene expression by affecting transcription process in vivo and in vitro. The current strategies for β-GT assay usually involve expensive equipment, laborious treatment, radioactive hazard, and poor sensitivity. Here, we report a Spinach-based fluorescent light-up biosensor for label-free measurement of β-GT activity by utilizing 5-hmC glucosylation-initiated rolling circle transcription amplification (RCTA)...

Chemically modified nucleic acid bases are sources of genomic instability and mutations but may also regulate gene expression as epigenetic or epitranscriptomic modifications. Depending on the cellular context, they can have vastly diverse impacts on cells, from mutagenesis or cytotoxicity to changing cell fate by regulating chromatin organisation and gene expression. Identical chemical modifications exerting different functions pose a challenge for the cell's DNA repair machinery, as it needs to accurately distinguish between epigenetic marks and DNA damage to ensure proper repair and maintenance of (epi)genomic integrity...

Methylation/demethylation of cytosines in DNA is central to epigenetics, which plays crucial roles in the regulation of about half of all human genes. Although the methylation mechanism, which downregulates gene expression, has been sufficiently decoded; the demethylation pathway, which upregulates gene expression, still holds questions to be answered. Demethylation of 5-methylcytosine by ten-eleven translocation (TET) enzymes yields understudied but epigenetically relevant intermediates, 5-hydroxymethyl (5-hmC), 5-formyl (5-fC), and 5-carboxyl (5-caC) cytosines...

Many epigenetic studies had found the decrease of 5-hydroxymethylcytosine (5-hmC) in various tumor tissues. However, limited information is available for hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). The present study aimd to investigate whether the decrease also existed in tumor tissues of HBV-related HCC and, if possible, to disclose its mechanism. We used immunohistochemistry and Image Pro Plus 6.0 Image Analysis Software to quantify the expression of 5-hmC, 5-methylcytosine, 10-eleven translocation (TET), isocitrate dehydrogenase (IDH) in pathological sections of tumor tissues and its para cancerous tissues of 40 HBV-related HCC patients...

Multiple sclerosis (MS) is a chronic disease affecting the central nervous system (CNS) due to an autoimmune attack on axonal myelin sheaths. Epigenetics is an open research topic on MS, which has been investigated in search of biomarkers and treatment targets for this heterogeneous disease. In this study, we quantified global levels of epigenetic marks using an ELISA-like approach in Peripheral Blood Mononuclear Cells (PBMCs) from 52 patients with MS, treated with Interferon beta (IFN-β) and Glatiramer Acetate (GA) or untreated, and 30 healthy controls...

Autologous mesenchymal stem/stromal cells (MSCs) have demonstrated important therapeutic effects in several diseases. Cardiovascular risk factors may impair MSC mitochondrial structure and function, but the underlying mechanisms remain unknown. We hypothesized that metabolic syndrome (MetS) induces epigenetic alterations in mitochondria-related genes in swine MSCs. Pigs were fed a Lean or MetS diet ( n = 6 each) for 16 weeks. MSCs were collected from subcutaneous abdominal fat, and DNA hydroxymethylation (5 hmC) profiles of mitochondria-related genes (MitoCarta-2...

Neuroblastoma is the most common extra-cranial solid tumor in childhood and epigenetic dysregulation is a key driver of this embryonal disease. In cell-free DNA from neuroblastoma patients with high-risk disease, we found increased 5-hydroxymethylcytosine (5-hmC) deposition on Polycomb Repressive Complex 2 (PRC2) target genes, a finding previously described in the context of bivalent genes. As bivalent genes, defined as genes bearing both activating (H3K4me3) and repressive (H3K27me3) chromatin modifications, have been shown to play an important role in development and cancer, we investigated the potential role of bivalent genes in maintaining a de-differentiated state in neuroblastoma and their potential use as a biomarker...

DNA 5-Hydroxymethylcytosine (5-hmC), an oxidative reaction mediated by the ten-eleven translocation (TET) family, has been reported to play an essential role in the progression of auto-inflammatory and autoimmune diseases. By far, little is known about the effect of DNA 5-hmC and the TET family on the development of Vogt-Koyanagi-Harada (VKH) disease. In this study, we discovered that the global DNA 5-hmC level and the TET activity were elevated in association with the up-regulated expression of TET2 at both mRNA and protein levels in CD4+ T cells from active VKH patients compared to healthy controls...

This study compares three different pretreatment protocols for the immunohistochemical detection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in nuclear DNA. The human biological samples analyzed included formalin-fixed and paraffin-embedded (FFPE) normal squamous epithelium, ethanol-fixed cultured cells, and metaphase chromosomes. The antigen retrieval methods included low pH Citrate and high pH Tris-ethylenediaminetetraacetic acid (EDTA) protocols, as well as a method using Pepsin pretreatment combined with HCl for DNA denaturation...

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are chemicals that are resistant to degradation and ubiquitous in our environments. PFAS may impact the developing epigenome, but current human evidence is limited to assessments of total DNA methylation. We assessed associations between first trimester PFAS exposures with newborn DNA methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC). DNA methylation mediation of associations between PFAS and birth outcomes were explored in the Michigan Mother Infant Pairs cohort...

The disease-residual transcriptomic profile (DRTP) within psoriatic healed/resolved skin and epidermal tissue-resident memory T (TRM) cells have been proposed to be crucial for the recurrence of old lesions. However, it is unclear whether epidermal keratinocytes are involved in disease recurrence. There is increasing evidence regarding the importance of epigenetic mechanisms in the pathogenesis of psoriasis. Nonetheless, the epigenetic changes that contribute to the recurrence of psoriasis remain unknown. The aim of this study was to elucidate the role of keratinocytes in psoriasis relapse...

Patients with advanced melanoma have shown an improved outlook after anti-PD1 therapy, but the low response rate restricts clinical benefit; therefore, enhancing anti-PD1 therapeutic efficacy remains a major challenge. Here, our findings showed a significantly increased abundance of α-KG in healthy controls, anti-PD1-sensitive melanoma-bearing mice, and anti-PD1-sensitive melanoma patients; moreover, supplementation with α-KG enhanced the efficacy of anti-PD1 immunotherapy and increased PD-L1 expression in melanoma tumors via STAT1/3...

Obesity is a major risk factor for colorectal cancer (CRC). Sustained hyperglycemia destabilizes tumor suppressor ten-eleven translocation (TET) 2, which is a substrate of AMPK, thereby dysregulating 5-hydroxymethylcytosine (5-hmC). However, the role played by this novel pathway in the development of obesity-related CRC is unclear. In this study, we aimed to evaluate the expression levels of TET2 and 5-hmC in obesity-related CRC and the effects of TET2 expression on the proliferation of CRC cells. To this end, surgically resected CRC samples from seven obese patients (Ob-CRC) and seven non-obese patients (nOb-CRC) were analyzed, and expression levels of the TET family and 5-hmC were compared between the groups...

Multidrug resistance is a major challenge in treating advanced hepatocellular carcinoma (HCC). Although recent studies have reported that the multidrug resistance phenotype is associated with abnormal DNA methylation in cancer cells, the epigenetic mechanism underlying multidrug resistance remains unknown. Here, we reported that the level of 5-hydroxymethylcytosine (5-hmC) in human HCC tissues was significantly lower than that in adjacent liver tissues, and reduced 5-hmC significantly correlated with malignant phenotypes, including poor differentiation and microvascular invasion; additionally, loss of 5-hmC was related to chemotherapy resistance in post-transplantation HCC patients...

BACKGROUND: Ischemic diseases represent a major global health care burden. Angiogenesis is critical in recovery of blood flow and repair of injured tissue in ischemic diseases. Ten-eleven translocation protein 2 (TET2), a member of DNA demethylases, is involved in many pathological processes. However, the role of TET2 in angiogenesis is still unrevealed. METHODS: TET2 was screened out from three DNA demethylases involved in 5-hydroxylmethylcytosine (5-hmC) regulation, including TET1, TET2 and TET3...