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Epigenetics Research

23:14 EDT 21st July 2018 | BioPortfolio

Genetics of Posttraumatic Stress Disorder (PTSD).

Post-traumatic stress disorder (PTSD) is a mental disorder following a severe traumatic experience and is characterized by high rates of comorbidity with related psychiatric disorders. However, even for individuals experiencing the same trauma, there is considerable inter-individual variability in the risk of PTSD, and this is largely thought to be determined by biological processes, such as genet...

Amino acid deprivation triggers a novel GCN2-independent response leading to the transcriptional reactivation of non-native DNA sequences.

In a variety of species, reduced food intake, and in particular protein or amino acid (AA) restriction, extends lifespan and healthspan. However, the underlying epigenetic and/or transcriptional mechanisms are largely unknown, and dissection of specific pathways in cultured cells may contribute to filling this gap. We have previously shown that, in mammalian cells, deprivation of essential AAs (me...

Epigenome Editing Enters the Arena: A New Tool to Reveal (and Reverse?) Pathologic Gene Regulation.

Reversal of epigenetic aberrations associated with the acquisition of doxorubicin resistance restores drug sensitivity in breast cancer cells.

Acquired resistance against doxorubicin is a major limitation in clinical treatment of breast cancer. The molecular mechanism behind the aberrant expression of genes leading to doxorubicin resistance is not clear. Epigenetic changes play an important role in the regulation of gene expression. Therefore, the objective of this study was to identify the epigenetic mechanism underlying acquired doxoru...

Early-life socioeconomic disadvantage, not current, predicts accelerated epigenetic aging of monocytes.

Low socioeconomic status (SES) in early-life and adulthood independently contribute to increased risk for aging-related chronic diseases. One mechanistic hypothesis for these associations involves faster cellular aging of immune cells, which could plausibly contribute to chronic disease pathogenesis by compromising host resistance and/or up-regulating inflammation. However, little is known about t...

Epigenetic regulation of intragenic transposable elements: A two-edged sword.

Genomes of animals and plants contain a large number of transposable elements (TEs). TEs often transpose into genic regions, affecting expression of surrounding genes. Intragenic TEs mostly reside in introns, and in much the same way as intergenic TEs, they are targeted by repressive epigenetic marks for transcriptional silencing. Silenced intragenic TEs generally co-repress expression of associat...

Triptolide inhibits Wnt signaling in NSCLC through upregulation of multiple Wnt inhibitory factors via epigenetic modifications to Histone H3.

In the last decade, it has become clear that epigenetic changes act together with genetic mutations to promote virtually every stage of tumorigenesis and cancer progression. This knowledge has triggered searches for "epigenetic drugs" that can be developed into new cancer therapies. Here we report that triptolide reduced lung cancer incidence from 70% to 10% in a Fen1 E160D transgenic mouse model ...

Impact of antipsychotic treatment on methylation status of Interleukin-6 IL-6 gene in Schizophrenia.

Immunopathogenesis of schizophrenia has emerged as one of the predominant research paradigms in recent times. Based on the altered serum levels as well as gene expression, IL-6 has been considered as a peripheral biomarker of schizophrenia. However, the precise mechanism underlying the altered expression of IL6 in schizophrenia is inadequately known. Given the profound influence of environmental f...

Quantitative epigenetics and evolution.

Epigenetics refers to chemical modifications of chromatin or transcribed DNA that can influence gene activity and expression without changes in DNA sequence. The last 20 years have yielded breakthroughs in our understanding of epigenetic processes that impact many fields of biology. In this review, we discuss how epigenetics relates to quantitative genetics and evolution. We argue that epigenetics...

Prenatal exposure to environmental insults and enhanced risk of developing Schizophrenia and Autism Spectrum Disorder: Focus on biological pathways and epigenetic mechanisms.

When considering neurodevelopmental disorders (NDDs), Schizophrenia (SZ) and Autism Spectrum Disorder (ASD) are considered to be among the most severe in term of prevalence, morbidity and impact on the society. Similar features and overlapping symptoms have been observed at multiple levels, suggesting common pathophysiological bases. Indeed, recent genome-wide association studies (GWAS) and epidem...

An epigenetic pacemaker is detected via a fast conditional expectation maximization algorithm.

DNA methylation has proven to be a remarkably accurate biomarker for human age, allowing the prediction of chronological age to within a couple of years. Recently, we proposed that the Universal PaceMaker (UPM), a flexible paradigm for modeling evolution, could be applied to epigenetic aging. Nevertheless, application to real data was restricted to small datasets for technical limitations.

Epigenome mapping of human normal purified hepatocytes: personal epigenome variation and genome-epigenome correlation.

The aim of this study was to reveal the epigenome landscape of human normal hepatocytes.

Epigenetic Control of Interleukin-9 in Asthma.

Trajectory analysis among African hominoids can provide insights into genetic and epigenetic influences during ontogeny.

Prior examination of the ontogeny of Hominoid talo-crural joint morphology using Singular Warp analysis suggested both a genetic and epigenetic signal during development. This question is examined using trajectory analysis and its implications for the Hominin fossil record explored.

A systematic review of epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma.

The objective of this systematic review is to identify and summarise studies which examine epigenetic biomarkers in patients with Barrett's oesophagus (BO) and their association with progression to oesophageal adenocarcinoma (OADC). BO is a precursor lesion for OADC. There is no clinical test to predict patients who are likely to progress to OADC. An epigenetic biomarker could predict patients who...

Single-cell epigenetics - Chromatin modification atlas unveiled by mass cytometry.

Modifications of histone proteins are fundamental to the regulation of epigenetic phenotypes. Dysregulations of histone modifications have been linked to the pathogenesis of diverse human diseases. However, identifying differential histone modifications in patients with immune-mediated diseases has been challenging, in part due to the lack of a powerful analytic platform to study histone modificat...

Resveratrol Reverts Epigenetic and Transcription Changes Caused by Smoke Inhalation on Bone-Related Genes in Rats.

We investigated the effects of cigarette smoke (CS) and resveratrol intake on the modulation of bone repair-related genes through epigenetic mechanisms at the global and gene-specific levels, after 30 days of calvarial defects were created, in rats. The samples were assigned to three groups as follows: no CS, CS, and CS/resveratrol. After evaluation of global (5 hmC) changes and epigenetic and t...

Marine Environmental Epigenetics.

Marine organisms' persistence hinges on the capacity for acclimatization and adaptation to the myriad of interacting environmental stressors associated with global climate change. In this context, epigenetics-mechanisms that facilitate phenotypic variation through genotype-environment interactions-are of great interest ecologically and evolutionarily. Our comprehensive review of marine environment...

Endometriosis: Perspective, lights, and shadows of etiology.

Endometriosis refers to the growth of ectopic endometrial tissue outside the uterine cavity. About 10-15% of female in reproductive age suffer from endometriosis. Several etiologies - such as oxidative stress, inflammatory factors and cytokines, genetic etiology, and hormone role - have been reported for endometriosis. Indeed, oxidative stress leads to abnormalities by the production of ROS and RN...

Small molecules as tools to study the chemical epigenetics of lysine acetylation.

Lysine acetylation has emerged as a key post-translational modification found at many sites throughout the cell. It plays an important role in epigenetic processes, and more generally in the regulation of protein stability and interactions. Acetyl groups are installed by lysine acetyltransferases and removed by lysine deacetylases. Acetylated lysine residues function as binding sites for bromodoma...

DNA Methylation in Radiation-Induced Carcinogenesis: Experimental Evidence and Clinical Perspectives.

Ionizing radiation is a valuable tool in many spheres of human life. At the same time, it is a genotoxic agent with a well-established carcinogenic potential. Progress achieved in the last two decades has demonstrated convincingly that ionizing radiation can also target the cellular epigenome. Epigenetics is defined as heritable changes in the expression of genes that are not due to alterations of...

Discovery of reversible DNA methyltransferase and lysine methyltransferase G9a inhibitors with antitumoral in vivo efficacy.

Using knowledge- and structure-based approaches, we designed and synthesized reversible chemical probes that simultaneously inhibit the activity of two epigenetic targets, histone 3 lysine 9 methyltransferase (G9a) and DNA methyltransferases (DNMT), at nanomolar ranges. Enzymatic competition assays confirmed our design strategy: substrate competitive inhibitors. Next, an initial exploration around...

Endothelial cell regulation through epigenetic mechanisms: depicting parallels and its clinical application within an intra-islet microenvironment.

The intra-islet endothelial cells (ECs), the building blocks of islet microvasculature, govern a number of cellular and pathophysiological processes associated with the pancreatic tissue. These cells are key to the angiogenic process and essential for islet revascularization after transplantation. Understanding fundamental mechanisms by which ECs regulate the angiogenic process is important as the...

Advances and Limitations of Current Epigenetic Studies Investigating Mammalian Axonal Regeneration.

Axonal regeneration relies on the expression of regenerative associated genes within a coordinated transcriptional programme, which is finely tuned as a result of the activation of several regenerative signalling pathways. In mammals, this chain of events occurs in neurons following peripheral axonal injury, however it fails upon axonal injury in the central nervous system, such as in the spinal c...

Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation.

Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromise...

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