scholarly journals Photoperiod-induced neurotransmitter plasticity declines with aging: an epigenetic regulation?

2019 ◽  
Author(s):  
Rory Pritchard ◽  
Helene Chen ◽  
Ben Romoli ◽  
Nicholas C. Spitzer ◽  
Davide Dulcis
Keyword(s):  
Dna Methylation ◽  
Histone Acetylation ◽  
Epigenetic Regulation ◽  
Synaptic Strength ◽  
Regulation Of Transcription ◽  
Epigenetic Mechanisms ◽  
Short Day ◽  
Age Dependent ◽  
Neurotransmitter Plasticity ◽  
Cell Phenotypes

ABSTRACTNeuroplasticity has classically been understood to arise through changes in synaptic strength or synaptic connectivity. A newly discovered form of neuroplasticity, neurotransmitter switching, involves changes in neurotransmitter identity. Chronic exposure to different photoperiods alters the number of dopamine (tyrosine hydroxylase, TH+) and somatostatin (SST+) neurons in the paraventricular nucleus (PaVN) of the hypothalamus of adult rats and results in discrete behavioral changes. Here we investigate whether photoperiod-induced neurotransmitter switching persists during aging and whether epigenetic mechanisms of histone acetylation and DNA methylation may contribute to this neurotransmitter plasticity. We show that this plasticity is robust at 1 and at 3 months but reduced in TH+ neurons at 12 months and completely abolished in both TH+ and SST+ neurons by 18 months. De novo methylation and histone 3 acetylation were observed following short-day photoperiod exposure in both TH+ and SST+ neurons at 1 and 3 months while an overall increase in methylation of SST+ neurons paralleled neuroplasticity reduction at 12 and 18 months. Histone acetylation increased in TH+ neurons and decreased in SST+ neurons following short-day exposure at 3 months while the total number of acetylated PaVN neurons remained constant. Reciprocal histone acetylation in TH+ and SST+ neurons suggests the importance of studying epigenetic regulation at the circuit level for identified cell phenotypes. The association of age-dependent reduction in neurotransmitter plasticity and changes in DNA methylation and acetylation patterns in two neuronal phenotypes known to switch transmitter identity suggests mechanistic insights into transmitter plasticity in the aging brain.SIGNIFICANCENeurotransmitter switching, like changes in synaptic strength, formation of new synapses and synapse remodeling, declines with age. This age-dependent reduction in transmitter plasticity is associated with changes in levels of DNA methylase and histone deacetylase that imply epigenetic regulation of transcription. A reciprocal pattern of histone acetylation in a single population of neurons that depends on the transmitter expressed emphasizes the value of studying epigenetic mechanisms at the level of cell phenotypes rather than cell genotypes or whole tissue. The findings may be useful for developing approaches for non-invasive treatment of disorders characterized by neurotransmitter dysfunction.

scholarly journals Early life stress induces age-dependent epigenetic changes in p11 gene expression in male mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mi Kyoung Seo ◽  
Jung Goo Lee ◽  
Sung Woo Park
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone Acetylation ◽  
Histone Methylation ◽  
Life Stress ◽  
Early Life ◽  
Age Groups ◽  
Early Life Stress ◽  
Epigenetic Modifications ◽  
Age Dependent

AbstractEarly life stress (ELS) causes long-lasting changes in gene expression through epigenetic mechanisms. However, little is known about the effects of ELS in adulthood, specifically across different age groups. In this study, the epigenetic modifications of p11 expression in adult mice subjected to ELS were investigated in different stages of adulthood. Pups experienced maternal separation (MS) for 3 h daily from postnatal day 1 to 21. At young and middle adulthood, behavioral test, hippocampal p11 expression levels, and levels of histone acetylation and methylation and DNA methylation at the hippocampal p11 promoter were measured. Middle-aged, but not young adult, MS mice exhibited increased immobility time in the forced swimming test. Concurrent with reduced hippocampal p11 levels, mice in both age groups showed a decrease in histone acetylation (AcH3) and permissive histone methylation (H3K4me3) at the p11 promoter, as well as an increase in repressive histone methylation (H3K27me3). Moreover, our results showed that the expression, AcH3 and H3Kme3 levels of p11 gene in response to MS were reduced with age. DNA methylation analysis of the p11 promoter revealed increased CpG methylation in middle-aged MS mice only. The results highlight the age-dependent deleterious effects of ELS on the epigenetic modifications of p11 transcription.

scholarly journals Leveraging brain cortex-derived molecular data to elucidate epigenetic and transcriptomic drivers of neurological function and disease

2018 ◽  
Author(s):  
Charlie Hatcher ◽  
Caroline L. Relton ◽  
Tom R. Gaunt ◽  
Tom G. Richardson
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Histone Acetylation ◽  
Genetic Variants ◽  
Large Scale ◽  
Genetic Variant ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Epigenetic Mechanisms ◽  
Trait Variation

AbstractIntegrative approaches which harness large-scale molecular datasets can help develop mechanistic insight into findings from genome-wide association studies (GWAS). We have performed extensive analyses to uncover transcriptional and epigenetic processes which may play a role in neurological trait variation.This was undertaken by applying Bayesian multiple-trait colocalization systematically across the genome to identify genetic variants responsible for influencing intermediate molecular phenotypes as well as neurological traits. In this analysis we leveraged high dimensional quantitative trait loci data derived from prefrontal cortex tissue (concerning gene expression, DNA methylation and histone acetylation) and GWAS findings for 5 neurological traits (Neuroticism, Schizophrenia, Educational Attainment, Insomnia and Alzheimer’s disease).There was evidence of colocalization for 118 associations suggesting that the same underlying genetic variant influenced both nearby gene expression as well as neurological trait variation. Of these, 73 associations provided evidence that the genetic variant also influenced proximal DNA methylation and/or histone acetylation. These findings support previous evidence at loci where epigenetic mechanisms may putatively mediate effects of genetic variants on traits, such as KLC1 and schizophrenia. We also uncovered evidence implicating novel loci in neurological disease susceptibility, including genes expressed predominantly in brain tissue such as MDGA1, KIRREL3 and SLC12A5.An inverse relationship between DNA methylation and gene expression was observed more than can be accounted for by chance, supporting previous findings implicating DNA methylation as a transcriptional repressor. Our study should prove valuable in helping future studies prioritise candidate genes and epigenetic mechanisms for in-depth functional follow-up analyses.

scholarly journals Epigenetic Mechanisms Involved in Cisplatin-Induced Nephrotoxicity: An Update

2021 ◽  
Vol 14 (6) ◽  
pp. 491
Author(s):  
Pía Loren ◽  
Nicolás Saavedra ◽  
Kathleen Saavedra ◽  
Tomás Zambrano ◽  
Patricia Moriel ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Death ◽  
Side Effects ◽  
Signaling Pathways ◽  
Solid Tumors ◽  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Epigenetic Mechanisms ◽  
Non Coding Rnas ◽  
New Strategies

Cisplatin is an antineoplastic drug used for the treatment of many solid tumors. Among its various side effects, nephrotoxicity is the most detrimental. In recent years, epigenetic regulation has emerged as a modulatory mechanism of cisplatin-induced nephrotoxicity, involving non-coding RNAs, DNA methylation and histone modifications. These epigenetic marks alter different signaling pathways leading to damage and cell death. In this review, we describe how different epigenetic modifications alter different pathways leading to cell death by apoptosis, autophagy, necroptosis, among others. The study of epigenetic regulation is still under development, and much research remains to fully determine the epigenetic mechanisms underlying cell death, which will allow leading new strategies for the diagnosis and therapy of this disease.

scholarly journals DNA Methylation Has a Local Effect on Transcription and Histone Acetylation

2002 ◽  
Vol 22 (19) ◽  
pp. 6689-6696 ◽  
Author(s):  
Ryan A. Irvine ◽  
Iping G. Lin ◽  
Chih-Lin Hsieh
Keyword(s):  
Dna Methylation ◽  
Histone Acetylation ◽  
Transcription Unit ◽  
Local Effect ◽  
Histone Deacetylation ◽  
Regulation Of Transcription ◽  
Coding Region ◽  
Transcriptional Suppression ◽  
The Impact ◽  
The Relationship

ABSTRACT DNA methylation is commonly associated with gene silencing, and a link between histone deacetylation and DNA methylation has been established. However, the transcriptional impact of the position and length of methylated zones relative to the promoter and the coding region of a gene remains quite unclear. This study investigates the impact of regional methylation on transcription and the relationship between DNA methylation and histone acetylation. Using patch-methylated stable episomes in human cells, we establish the pivotal importance of the location of DNA methylation in the regulation of transcription. We further demonstrate that the size of the methylated patch is not a key determinant for transcriptional suppression. The impact of DNA methylation on transcription is greater when it is in the transcription unit, and it is primarily a local effect. However, methylation outside of the transcription unit may potentiate the effect of methylation within the transcription unit. Acetylated histones are associated with unmethylated DNA and are nearly absent from methylated DNA regions. This association appears to be local and does not propagate along the DNA.

Epigenetics in Liver Fibrosis

2017 ◽  
Vol 37 (03) ◽  
pp. 219-230 ◽  
Author(s):  
Veronica Massey ◽  
Joaquin Cabezas ◽  
Ramon Bataller
Keyword(s):  
Dna Methylation ◽  
Liver Fibrosis ◽  
Epigenetic Regulation ◽  
Cell Activation ◽  
Stellate Cell ◽  
Epigenetic Mechanisms ◽  
Epigenetic Landscape ◽  
Chronic Liver Injury ◽  
Novel Biomarkers ◽  
Disease Specific

AbstractLiver fibrosis is a common consequence of chronic liver injury and is a key determinant of liver-associated morbidity and mortality. Identification of new mechanisms of fibrosis, including disease-specific molecular drivers, remains relevant to reveal novel biomarkers and therapeutic targets. Recently, greater accessibility to more advanced molecular methods that can assess changes in epigenetic regulation has stimulated more research investigating the epigenetic landscape of liver fibrosis. Such studies have revealed changes in DNA methylation, histone acetylation, and microRNAs that regulate the fibrogenic response to injury including hepatic stellate cell activation. The aim of this review is to briefly introduce the general mechanisms and epigenetic regulation of liver fibrosis and to familiarize the reader with the chief epigenetic mechanisms implicated as drivers of liver fibrosis.

scholarly journals Epigenetic Regulation of Glycosylation in Cancer and Other Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 2980
Author(s):  
Rossella Indellicato ◽  
Marco Trinchera
Keyword(s):  
Dna Methylation ◽  
Inflammatory Bowel Disease ◽  
Transcription Factors ◽  
Epigenetic Regulation ◽  
Bowel Disease ◽  
Noncoding Rnas ◽  
Fine Tuning ◽  
Epigenetic Mechanisms ◽  
Complex Process ◽  
Inflammatory Bowel

In the last few decades, the newly emerging field of epigenetic regulation of glycosylation acquired more importance because it is unraveling physiological and pathological mechanisms related to glycan functions. Glycosylation is a complex process in which proteins and lipids are modified by the attachment of monosaccharides. The main actors in this kind of modification are the glycoenzymes, which are translated from glycosylation-related genes (or glycogenes). The expression of glycogenes is regulated by transcription factors and epigenetic mechanisms (mainly DNA methylation, histone acetylation and noncoding RNAs). This review focuses only on these last ones, in relation to cancer and other diseases, such as inflammatory bowel disease and IgA1 nephropathy. In fact, it is clear that a deeper knowledge in the fine-tuning of glycogenes is essential for acquiring new insights in the glycan field, especially if this could be useful for finding novel and personalized therapeutics.

scholarly journals Epigenetic regulation of peroxiredoxins: Implications in the pathogenesis of cancer

2016 ◽  
Vol 242 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Suet-Hui Ow ◽  
Pei-Jou Chua ◽  
Boon-Huat Bay
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Histone Deacetylases ◽  
Epigenetic Mechanisms ◽  
Epigenetic Regulators ◽  
Future Treatments ◽  
Peroxiredoxin I ◽  
Reversible Nature

Peroxiredoxin I to VI (PRX I–VI), a family of highly conserved antioxidants, has been implicated in numerous diseases. There have been reports that PRXs are expressed aberrantly in a variety of tumors, implying that they could play an important role in carcinogenesis. Epigenetic mechanisms such as DNA methylation, histone modifications, and microRNAs have been reported to modulate expression of PRXs. In addition, the use of epigenetic regulators, such as histone deacetylases, has been demonstrated to restore PRX to normal levels, indicating that the reversible nature of epigenetics can be exploited for future treatments.

scholarly journals Feasible strategies for studying the involvement of DNA methylation and histone acetylation in the stress-induced formation of quality-related metabolites in tea (Camellia sinensis)

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jie Yang ◽  
Dachuan Gu ◽  
Shuhua Wu ◽  
Xiaochen Zhou ◽  
Jiaming Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Acetylation ◽  
Secondary Metabolism ◽  
Regulatory Mechanisms ◽  
Epigenetic Mechanisms ◽  
Research Strategies ◽  
Metabolism Regulation ◽  
Growth Development ◽  
Regulatory Effects ◽  
Tea Plants

AbstractTea plants are subjected to multiple stresses during growth, development, and postharvest processing, which affects levels of secondary metabolites in leaves and influences tea functional properties and quality. Most studies on secondary metabolism in tea have focused on gene, protein, and metabolite levels, whereas upstream regulatory mechanisms remain unclear. In this review, we exemplify DNA methylation and histone acetylation, summarize the important regulatory effects that epigenetic modifications have on plant secondary metabolism, and discuss feasible research strategies to elucidate the underlying specific epigenetic mechanisms of secondary metabolism regulation in tea. This information will help researchers investigate the epigenetic regulation of secondary metabolism in tea, providing key epigenetic data that can be used for future tea genetic breeding.

scholarly journals The Epigenetic Regulation of Microenvironment in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Fang Wang ◽  
Greg Malnassy ◽  
Wei Qiu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Epigenetic Regulation ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Epigenetic Mechanisms ◽  
Non Coding Rnas

Hepatocellular carcinoma (HCC) is a highly lethal and complex malignancy strongly influenced by the surrounding tumor microenvironment. The HCC microenvironment comprises hepatic stellate cells (HSCs), tumor-associated macrophages (TAMs), stromal and endothelial cells, and the underlying extracellular matrix (ECM). Emerging evidence demonstrates that epigenetic regulation plays a crucial role in altering numerous components of the HCC tumor microenvironment. In this review, we summarize the current understanding of the mechanisms of epigenetic regulation of the microenvironment in HCC. We review recent studies demonstrating how specific epigenetic mechanisms (DNA methylation, histone regulation, and non-coding RNAs mediated regulation) in HSCs, TAMs, and ECM, and how they contribute to HCC development, so as to gain new insights into the treatment of HCC via regulating epigenetic regulation in the tumor microenvironment.

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