scholarly journals DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation

2021 ◽  
Author(s):  
Assia Tiane ◽  
Melissa Schepers ◽  
Renzo Riemens ◽  
Ben Rombaut ◽  
Patrick Vandormael ◽  
...  
Keyword(s):  
Dna Methylation ◽  
State Of The Art ◽  
Transcriptional Regulators ◽  
Dna Binding Protein ◽  
Epigenetic Mechanisms ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor ◽  
Myelin Disorders ◽  
Epigenetic Editing ◽  
Gene Expression Levels

AbstractThe differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes is the prerequisite for remyelination in demyelinated disorders such as multiple sclerosis (MS). Epigenetic mechanisms, such as DNA methylation, have been suggested to control the intricate network of transcription factors involved in OPC differentiation. Yet, the exact mechanism remains undisclosed. Here, we are the first to identify the DNA-binding protein inhibitors, Id2 and Id4, as targets of DNA methylation during OPC differentiation. Using state-of-the-art epigenetic editing via CRISPR/dCas9-DNMT3a, we confirm that targeted methylation of Id2/Id4 drives OPC differentiation. Moreover, we show that in the pathological context of MS, methylation and gene expression levels of both ID2 and ID4 are altered compared to control human brain samples. We conclude that DNA methylation is crucial to suppress ID2 and ID4 during OPC differentiation, a process that appears to be dysregulated during MS. Our data do not only reveal new insights into oligodendrocyte biology, but could also lead to a better understanding of CNS myelin disorders.

scholarly journals Physiological, molecular and genetic aspects of alpha-synuclein and its correlation with high alcohol consumption

2019 ◽  
Vol 67 (3) ◽  
pp. 315-322
Author(s):  
Tania Yadira Martínez-Rodríguez ◽  
Mauricio Rey-Buitrago
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Alcohol Consumption ◽  
State Of The Art ◽  
Alpha Synuclein ◽  
Current Evidence ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
High Alcohol ◽  
High Alcohol Consumption

Introduction: Significant changes in the expression of α-synuclein (SNCA) can be seen in subjects with high alcohol consumption, altering neuroprotection and causing changes in the reward system.Objective: To present state-of-the-art studies on the physiological, molecular and genetic aspects of SNCA related to high alcohol consumption.Materials and methods: A search of records published from 2007 to 2017 was carried out in PUBMED, ScienceDirect and Cochrane with the terms alpha-synuclein, alcoholism, genetic polymorphism, gene expression, DNA methylation and molecular biology.Results: The search yielded 1 331 references, of which 51 full-texts were selected. The results describe the current evidence of the physiological and pathological aspects of α-synuclein (SNCA) and the genetic and epigenetic changes related to its expression in people with high alcohol consumption.Conclusions: The evidence suggests that a differential expression of α-synuclein (SNCA) is found in subjects with high alcohol consumption, as a result of modifications in the genetic and epigenetic mechanisms, leading to physipathological neuroadaptations. SNCA is a promising marker in the field of alcoholism research; therefore, more studies are required in this regard, taking into account the genetic heterogeneity of each population.

Neuroinflammation in Demyelinating Diseases: Oxidative Stress as a Modulator of Glial Cross-Talk

2020 ◽  
Vol 25 (45) ◽  
pp. 4755-4762 ◽  
Author(s):  
Rodrigo Varas ◽  
Fernando C. Ortiz
Keyword(s):  
Oxidative Stress ◽  
Action Potentials ◽  
Cell Interaction ◽  
Demyelinating Diseases ◽  
Signal Molecules ◽  
Oligodendrocyte Precursor Cells ◽  
Cytokines And Chemokines ◽  
Regulatory Aspect ◽  
Saltatory Conduction ◽  
Oligodendrocyte Precursor

: Myelin is a specialized membrane allowing for saltatory conduction of action potentials in neurons, an essential process to achieve the normal communication across the nervous system. Accordingly, in diseases characterized by the loss of myelin and myelin forming cells -oligodendrocytes in the CNS-, patients show severe neurological disabilities. After a demyelinated insult, microglia, astrocytes and oligodendrocyte precursor cells invade the lesioned area initiating a spontaneous process of myelin repair (i.e. remyelination). A preserved hallmark of this neuroinflammatory scenario is a local increase of oxidative stress, where several cytokines and chemokines are released by glial and other cells. This generates an environment that determines cell interaction resulting in oligodendrocyte maturity and the ability to synthesize new myelin. Herein we review the main features of the regulatory aspect of these molecules based on recent findings and propose new putative signal molecules involved in the remyelination process, focused in the etiology of Multiple Sclerosis, one of the main demyelinating diseases causing disabilities in the population.

Epigenetic Mechanisms of Maternal Dietary Protein and Amino Acids Affecting Growth and Development of Offspring

2019 ◽  
Vol 20 (7) ◽  
pp. 727-735 ◽  
Author(s):  
Yi Wu ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma
Keyword(s):  
Amino Acids ◽  
Dna Methylation ◽  
Dietary Protein ◽  
Growth And Development ◽  
Later Life ◽  
Biological Macromolecules ◽  
Epigenetic Mechanisms ◽  
Maternal Circulation ◽  
Energy Processing ◽  
Living Organisms

Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring’s later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body’s one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.

Epigenetics, Nutrition, Disease and Drug Development

2019 ◽  
Vol 16 (4) ◽  
pp. 386-391 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Dna Methylation ◽  
Drug Discovery ◽  
Rna Interference ◽  
Nutritional Requirements ◽  
Signal Pathways ◽  
Disease Development ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Health And Disease ◽  
Novel Drug

Epigenetic mechanisms comprising of DNA methylation, histone modifications and gene silencing by RNA interference have been strongly linked to the development and progression of various diseases. These findings have triggered research on epigenetic functions and signal pathways as targets for novel drug discovery. Dietary intake has also presented significant influence on human health and disease development and nutritional modifications have proven important in prevention, but also the treatment of disease. Moreover, a strong link between nutrition and epigenetic changes has been established. Therefore, in attempts to develop novel safer and more efficacious drugs, both nutritional requirements and epigenetic mechanisms need to be addressed.

scholarly journals New Aspects of the Epigenetics of Pancreatic Carcinogenesis

Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 18
Author(s):  
Murat Toruner ◽  
Martin E. Fernandez-Zapico ◽  
Christopher L. Pin
Keyword(s):  
Pancreatic Cancer ◽  
Dna Methylation ◽  
Survival Rate ◽  
Epigenetic Mechanisms ◽  
Therapeutic Approaches ◽  
Cancer Epigenetics ◽  
Pancreatic Carcinogenesis ◽  
New Therapeutic Approaches ◽  
Environmental Events ◽  
Underlying Pathogenesis

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy.

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