Epigenome

The Fontan operation is the current standard of care for single-ventricle congenital heart disease. Individuals with a Fontan circulation (FC) exhibit central venous hypertension and face life-threatening complications of hepatic fibrosis, known as Fontan-associated liver disease (FALD). The fundamental biology and mechanisms of FALD are little understood. Here, we generated a transcriptomic and epigenomic atlas of human FALD at single-cell resolution using multiomic snRNA-ATAC-seq. We found profound cell type-specific transcriptomic and epigenomic changes in FC livers...

Epigenetic editing, also known as EpiEdit, offers an exciting way to control gene expression without altering the DNA sequence. In this study, we evaluate the application of EpiEdit to plant promoters, specifically the MLO (mildew locus o) gene promoter. We use a modified CRISPR-(d)Cas9 system, in which the nuclease-deficient Cas9 (dCas9) is fused to an epigenetic modifier, to experimentally demonstrate the utility of this tool for optimizing epigenetic engineering of a plant promoter prior to in vivo plant epigenome editing...

PURPOSE OF REVIEW: To review what is currently known about the pathogenesis, diagnosis, treatment, and prevention of acute rejection (AR) in lung transplantation. RECENT FINDINGS: Epigenomic and transcriptomic methods are gaining traction as tools for earlier detection of AR, which still remains primarily a histopathologic diagnosis. SUMMARY: Acute rejection is a common cause of early posttransplant lung graft dysfunction and increases the risk of chronic rejection...

Ikaros is a transcriptional factor required for conventional T cell development, differentiation, and anergy. While the related factors Helios and Eos have defined roles in regulatory T cells (Treg), a role for Ikaros has not been established. To determine the function of Ikaros in the Treg lineage, we generated mice with Treg-specific deletion of the Ikaros gene ( Ikzf1 ). We find that Ikaros cooperates with Foxp3 to establish a major portion of the Treg epigenome and transcriptome. Ikaros-deficient Treg exhibit Th1-like gene expression with abnormal production of IL-2, IFNg, TNFa, and factors involved in Wnt and Notch signaling...

No abstract text is available yet for this article.

Gut microbiota interacts with host epithelial cells and regulates many physiological functions such as genetics, epigenetics, metabolism of nutrients, and immune functions. Dietary factors may also be involved in the etiology of colorectal cancer (CRC), especially when an unhealthy diet is consumed with excess calorie intake and bad practices like smoking or consuming a great deal of alcohol. Bacteria including Fusobacterium nucleatum, Enterotoxigenic Bacteroides fragilis (ETBF), and Escherichia coli ( E. coli ) actively participate in the carcinogenesis of CRC...

No abstract text is available yet for this article.

Early-life adversity as neglect or low socioeconomic status is associated with negative physical/mental health outcomes and plays an important role in health trajectories through life. The early-life environment has been shown to be encoded as changes in epigenetic markers that are retained for many years.We investigated the effect of maternal major financial problems (MFP) and material deprivation (MD) on their children's epigenome in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Epigenetic aging, measured with epigenetic clocks, was weakly accelerated with increased MFP...

PURPOSE OF REVIEW: Gastrointestinal mucositis (GIM) is a significant complication of cancer therapy. Whilst inflammation is a central feature of GIM, studies attempting to mitigate mucosal damage via this mechanism are scarce. This review describes the relation between GIM, local and systemic inflammation, and the microbiome and its metabolites, and explores recent research on therapeutics that target this relationship. RECENT FINDINGS: Recent literature underscores the pivotal role of inflammation in GIM, elucidating its bidirectional relation with disturbance of the gut microbiota composition and intestinal permeability...

BACKGROUND: One of the mechanisms regulating the biological activity of tumor necrosis factor (TNF) in cells is the co-expression of TNFR1/TNFR2 receptors. A model with a differential level of receptor expression is required to evaluate the contribution of these mechanisms. AIM: The development of a cellular model to compare the effects of TNF on cells depending on the presence of both receptors and TNFR2 alone. METHODS: TNFR1 absence modifications of ZR-75/1 and K-562 cell lines were obtained by TNFR1 knockout...

Alzheimer's Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects of AD's pathogenesis that may contribute to drug repurposing efforts by integrating DNA methylation and genetic data. Implementing the network-based tool, a dense module search of genome-wide association studies (dmGWAS), we integrated a large-scale GWAS dataset with DNA methylation data to identify gene network modules associated with AD. Our analysis yielded 286 significant gene network modules...

The effects of PM2.5 on human health fluctuate greatly among various age groups, influenced by a range of physiological and immunological reactions. This paper compares the pathogenesis of the disease caused by PM2.5 in people of different ages, focusing on how children, adults, and the elderly are each susceptible to it because of differences in their bodies. Regarding children, exposure to PM2.5 is linked to many negative consequences. These factors consist of inflammation, oxidative stress, and respiratory problems, which might worsen pre-existing conditions and potentially cause neurotoxicity and developmental issues...

Dengue viruses (DENV) are positive-stranded RNA viruses belonging to the Flaviviridae family. DENV is the causative agent of dengue, the most rapidly spreading viral disease transmitted by mosquitoes. Each year, millions of people contract the virus through bites from infected female mosquitoes of the Aedes species. In the majority of individuals, the infection is asymptomatic, and the immune system successfully manages to control virus replication within a few days. Symptomatic individuals may present with a mild fever (Dengue fever or DF) that may or may not progress to a more critical disease termed Dengue hemorrhagic fever (DHF) or the fatal Dengue shock syndrome (DSS)...

Vasospasm is a potentially preventable cause of poor prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH). Epigenetics might provide insight on its molecular mechanisms. We aimed to analyze the association between differential DNA methylation (DNAm) and development of vasospasm. We conducted an epigenome-wide association study in 282 patients with aSAH admitted to our hospital. DNAm was assessed with the EPIC Illumina chip (> 850 K CpG sites) in whole-blood samples collected at hospital admission...

Handgrip strength is a crucial indicator to monitor the change of cognitive function over time, but its mechanism still needs to be further explored. We sampled 59 monozygotic twin pairs to explore the potential mediating effect of DNA methylation (DNAm) on the association between handgrip strength and cognitive function. The initial step was the implementation of an epigenome-wide association analysis (EWAS) in the study participants, with the aim of identifying DNAm variations that are associated with handgrip strength...

Aversive caregiving in early life is a risk factor for aberrant brain and behavioral development. This outcome is related to epigenetic dysregulation of the brain-derived neurotrophic factor (Bdnf) gene. The Bdnf gene encodes for BDNF, a neurotrophin involved in early brain development, neural plasticity, learning, and memory. Recent work suggests that exercise may be neuroprotective in part by supporting BDNF protein and gene expression, making it an exciting target for therapeutic interventions. To our knowledge, exercise has never been studied as a therapeutic intervention in preclinical rodent models of caregiver maltreatment...

Genome-wide association studies have revealed >270 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the molecular determinants behind this psychiatric condition. Epigenetic marks such as post-translational histone modifications remain largely plastic during development and adulthood, allowing a dynamic impact of environmental factors, including antipsychotic medications, on access to genes and regulatory elements. However, few studies so far have profiled cell-specific genome-wide histone modifications in postmortem brain samples from schizophrenia subjects, or the effect of antipsychotic treatment on such epigenetic marks...

SUMMARY: Chromatin accessibility serves as a critical measurement of physical contact between nuclear macromolecules and DNA sequence, providing valuable insights into the comprehensive landscape of regulatory mechanisms, thus we previously developed the OpenAnnotate web server. However, as an increasing number of epigenomic analysis software tools emerged, web-based annotation often faced limitations and inconveniences when integrated into these software pipelines. To address these issues, we here develop two software packages named OpenAnnotatePy and OpenAnnotateR...

Brain-derived neurotrophic factor (BDNF), a key neurotrophin within the brain, by selectively activating the TrkB receptor, exerts multimodal effects on neurodevelopment, synaptic plasticity, cellular integrity and neural network dynamics. In parallel, glucocorticoids (GCs), vital steroid hormones, which are secreted by adrenal glands and rapidly diffused across the mammalian body (including the brain), activate two different groups of intracellular receptors, the mineralocorticoid and the glucocorticoid receptors, modulating a wide range of genomic, epigenomic and postgenomic events, also expressed in the neural tissue and implicated in neurodevelopment, synaptic plasticity, cellular homeostasis, cognitive and emotional processing...

Our understanding of the sex-specific role of the non-coding genome in serious mental illness remains largely incomplete. To address this gap, we explored sex differences in 1,393 chromatin accessibility profiles, derived from neuronal and non-neuronal nuclei of two distinct cortical regions from 234 cases with serious mental illness and 235 controls. We identified sex-specific enhancer-promoter interactions and showed that they regulate genes involved in X-chromosome inactivation (XCI). Examining chromosomal conformation allowed us to identify sex-specific cis - and trans -regulatory domains (CRDs and TRDs)...