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Epigenetics Research

07:24 EDT 21st October 2018 | BioPortfolio

Epigenetic ageing is distinct from senescence-mediated ageing and is not prevented by telomerase expression.

The paramount role of senescent cells in ageing has prompted suggestions that re-expression of telomerase may prevent ageing; a proposition that is predicated on the assumption that senescent cells are the sole cause of ageing. Recently, several DNA methylation-based age estimators (epigenetic clocks) have been developed and they revealed that increased epigenetic age is associated with a host of ...

Racheting Up Repair.

In this issue of Immunity, Daniel et al. (2018a) demonstrate that the nuclear receptor PPARγ acts in a ligand-insensitive manner to impart transcriptional memory and enhanced functionality to IL-4 polarized macrophages. Their findings shed light on the mechanisms that control priming of the epigenome in response to inflammatory signals.

Analytical epigenetics: single-molecule optical detection of DNA and histone modifications.

The field of epigenetics describes the relationship between genotype and phenotype, by regulating gene expression without changing the canonical base sequence of DNA. It deals with molecular genomic information that is encoded by a rich repertoire of chemical modifications and molecular interactions. This regulation involves DNA, RNA and proteins that are enzymatically tagged with small molecular ...

EWASdb: epigenome-wide association study database.

DNA methylation, the most intensively studied epigenetic modification, plays an important role in understanding the molecular basis of diseases. Furthermore, epigenome-wide association study (EWAS) provides a systematic approach to identify epigenetic variants underlying common diseases/phenotypes. However, there is no comprehensive database to archive the results of EWASs. To fill this gap, we de...

Major trauma and acceleration of the ageing process.

It is well established that numerous factors can affect the rate at which we age biologically. Diet, physical activity, lifestyle and our genes all play a major role in influencing the ageing trajectory and longevity. Major trauma affects millions globally, is the major cause of death in young adults and could influence ageing processes but has largely been ignored by biogenterologists. The long-t...

Angiotensin II induced CSF1 transcription is mediated by a crosstalk between different epigenetic factors in vascular endothelial cells.

Endothelium-derived colony stimulating factor (CSF1) plays a key role in a range of human pathologies. Angiotensin II (Ang II) has been documented to stimulate CSF1 transcription although the underlying epigenetic mechanism remains unclear. Here we report that induction of CSF1 transcription by Ang II in vascular endothelial cells paralleled alterations of signature histone modifications surroundi...

Cross Talk Between Aluminum and Genetic Susceptibility and Epigenetic Modification in Alzheimer's Disease.

This chapter primarily focuses on two key aspects related to aluminum neurotoxicity and its mechanism in Alzheimer's disease (AD), which are genetic susceptibility and epigenetic modification. The toxicity of aluminum has been confirmed from plant experiments, animal experiments, in vitro experiments, and epidemiological studies. However, the mechanisms underlying this phenomenon have largely rema...

Acceleration of cancer science with genome editing and related technologies.

Genome editing includes various edits of the genome, such as short insertions and deletions, substitutions, and chromosomal rearrangements including inversions, duplications, and translocations. These varieties are based on single or multiple DNA double strand break (DSB)-triggered in cellulo repair machineries. In addition to these "conventional" genome editing strategies, tools enabling customiz...

H3K9me3 and H4K20me3 represent the epigenetic landscape for 53BP1 binding to DNA lesions.

Methylation of histones H4 at lysine 20 position (H4K20me), which is functional in DNA repair, represents a binding site for the 53BP1 protein. Here, we show a radiation-induced increase in the level of H4K20me3 while the levels of H4K20me1 and H4K20me2 remained intact. H4K20me3 was significantly pronounced at DNA lesions in only the G1 phase of the cycle, while this histone mark was reduced in ve...

SETD2-dependent H3K36me3 plays a critical role in epigenetic regulation of the HPV31 life cycle.

The life cycle of HPV is tied to the differentiation status of its host cell, with productive replication, late gene expression and virion production restricted to the uppermost layers of the stratified epithelium. HPV DNA is histone-associated, exhibiting a chromatin structure similar to that of the host chromosome. Although HPV chromatin is subject to histone post-translational modifications, ho...

Epigenetic Soluble Epoxide Hydrolase Regulation Causes Endothelial Dysfunction.

A novel epigenetic regulator, Jarid1b (KDM5B), that contributes to increasing vascular soluble epoxide hydrolase (sEH) protein expression and impairing endothelial function was identified by Vasconez et al. in this edition of Acta Physiologica. Elevated angiotensin II levels contribute to several cardiovascular diseases and endothelial dysfunction in hypertension. Endothelial dysfunction in angio...

Natural variability and modulation by environmental stressors of global genomic cytosine methylation levels in a freshwater crustacean, Gammarus fossarum.

To improve the assessment of aquatic organism responses to environmental stressors, there is an interest in studying epigenetic marks in addition to other validated biomarkers. Indeed, the epigenetic marks may be influenced by the surrounding environment. Non-model invertebrates such as gammarids are sentinel organisms representative of the diversity of natural stream communities. Despite their ec...

Are DNA damage response kinases a target for the differentiation treatment of acute myeloid leukemia?

Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy characterized by the expansion of hematopoietic stem/progenitor cells (HPCs) blocked at different stages of maturation/differentiation. The poor outcome of AMLs necessitates therapeutic improvement. In AML, genes encoding for myeloid transcription factors, signaling receptors regulating cell proliferation, and epigenetic modifi...

Epigenetic dynamic during endochondral ossification and articular cartilage development.

Within the last decade epigenetics has emerged as fundamental regulator of numerous cellular processes, including those orchestrating embryonic and fetal development. As such, epigenetic factors play especially crucial roles in endochondral ossification, the process by which bone tissue is created, as well during articular cartilage formation. In this review, we summarize the recent discoveries th...

Repurposing enzymatic transferase reactions for targeted labeling and analysis of DNA and RNA.

Produced as linear biopolymers from four major types of building blocks, DNA and RNA are further furnished with a range of covalent modifications. Despite the impressive specificity of natural enzymes, the transferred groups are often poor reporters and not amenable to further derivatization. Therefore, strategies based on repurposing some of these enzymatic reactions to accept derivatized version...

Natural regulatory plasma cells.

B cells can generate several types of antibody-secreting cells, including plasmablasts that divide and are short lived, as well as plasma cells that do not proliferate and can persist for extended time periods. Here, we discuss the identification of a novel subset of non-dividing plasma cells specialized in the production of interleukin(IL)-10. These cells develop at steady state, including in ger...

Genome-wide methylation analysis identifies ELOVL5 as an epigenetic biomarker for the risk of type 2 diabetes mellitus.

Genome-wide DNA methylation has been implicated in complex human diseases. Here, we identified epigenetic biomarkers for type 2 diabetes (T2D) underlying obesogenic environments. In a blood-based DNA methylation analysis of 11 monozygotic twins (MZTW) discordant for T2D, we discovered genetically independent candidate methylation sites. In a follow-up replication study (17 MZTW pairs) for external...

The epigenetic landscape in the cardiovascular complications of diabetes.

A growing body of evidence suggests that epigenetic modifications-changes to the genome that do not involve changes in DNA sequence-may significantly derail transcriptional programs implicated in angiogenesis, oxidative stress and inflammation, thus fostering cardiovascular damage in patients with diabetes. Notably, adverse epigenetic signals acquired over the life course can be transmitted to the...

Maternal L-Carnitine supplementation ameliorates renal underdevelopment and epigenetic changes in male mice offspring due to maternal smoking.

Epidemiological and animal studies showed that L-carnitine (LC) supplementation can ameliorate oxidative stress-induced tissues damage. We have previously shown that maternal cigarette smoke exposure (SE) can increase renal oxidative stress in newborn offspring with postnatal kidney underdevelopment and renal dysfunction in adulthood, which were normalised by LC administration in the SE dams durin...

EFFECTS OF THE PESTICIDE CHLORPYRIFOS ON BREAST CANCER DISEASE. IMPLICATION OF EPIGENETIC MECHANISMS.

Chlorpyrifos (CPF) is an organophosphorus pesticide used for agricultural pest control all over the world. We have previously demonstrated that environmental concentrations of this pesticide alter mammary gland histological structure and hormonal balance in rats chronically exposed. In this work, we analyzed the effects of CPF on mammary tumors development. Our results demonstrated that CPF increa...

Impact of ZBTB7A hypomethylation and expression patterns on treatment response to hydroxyurea.

We aimed to clarify the emerging epigenetic landscape in a group of genes classified as "modifier genes" of the β-type globin genes (HBB cluster), known to operate in trans to accomplish the two natural developmental switches in globin expression, from embryonic to fetal during the first trimester of conception and from fetal to adult around the time of birth. The epigenetic alterations were dete...

AMPK Regulates the Epigenome through Phosphorylation of TET2.

Emerging evidence suggests that changes to cellular metabolism can regulate epigenetic modifications to alter gene expression. Recently in Nature, Wu et al. show that the metabolic regulator AMPK can phosphorylate and thus stabilize the epigenetic modifying enzyme TET2, defining a novel signaling link between metabolism and the epigenome.

Functional characterization of the Sox2, c-Myc, and Oct4 promoters.

To better understand the mechanisms in transcriptional regulation, we analyzed the promoters of the reprogramming key genes Sox2, c-Myc, and Oct4. Here, we cloned different 5' deletions of the goat Sox2, c-Myc, and Oct4 promoters, and evaluated their functions by green fluorescent protein reporter system and dual-luciferase reporter system. Site-directed mugagenesis and epigenetic modifiers were u...

Diseases of the oral cavity in light of the newest epigenetic research: Possible implications for stomatology.

Epigenetics is the study of inheritable changes in gene expression without changes in the underlying deoxyribonucleic acid (DNA) sequence. The main mechanisms of epigenetic regulation include DNA methylation, modifications in histones, and micro-ribonucleic acids (miRNA). Recent research evidence has shown that environmental and lifestyle factors dynamically interact with the genome, influencing e...

Thermal Response of Epigenetic Genes Informs Turtle Sex Determination with and without Sex Chromosomes.

Vertebrate sexual fate can be established by environmental cues (e.g., temperature-dependent sex determination, TSD) or by genetic content (genotypic sex determination, GSD). While methylation is implicated in TSD, the influence of broader epigenetic processes in sexual development remains obscure. Here, we investigated for the first time the embryonic gonadal expression of the genome-wide epigene...

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