Abstract:The chromatin landscape has acquired deep attention from several fields ranging from cell biology to neurological and psychiatric diseases. The role that DNA modifications have on gene expression regulation has become apparent in several physiological processes, and numerous efforts have been performed to establish a relationship between DNA modifications and physiological conditions, such as cognitive performance and aging. DNA modifications are incorporated by specific sets of enzymes—the writers—and the mod… Show more
“…The reaction, firstly, consists of the oxidation of 5-mC to 5-hydroxymethylcytosine (5-hmC). Consequently, the TETs continue the oxidation of 5-hmC to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC) [ 19 , 20 ]. Among the TET family are the proteins Tet1, Tet2 and Tet3.…”
Aging is an inevitable outcome of life, characterized by a progressive decline in tissue and organ function. At a molecular level, it is marked by the gradual alterations of biomolecules. Indeed, important changes are observed on the DNA, as well as at a protein level, that are influenced by both genetic and environmental parameters. These molecular changes directly contribute to the development or progression of several human pathologies, including cancer, diabetes, osteoporosis, neurodegenerative disorders and others aging-related diseases. Additionally, they increase the risk of mortality. Therefore, deciphering the hallmarks of aging represents a possibility for identifying potential druggable targets to attenuate the aging process, and then the age-related comorbidities. Given the link between aging, genetic, and epigenetic alterations, and given the reversible nature of epigenetic mechanisms, the precisely understanding of these factors may provide a potential therapeutic approach for age-related decline and disease. In this review, we center on epigenetic regulatory mechanisms and their aging-associated changes, highlighting their inferences in age-associated diseases.
“…The reaction, firstly, consists of the oxidation of 5-mC to 5-hydroxymethylcytosine (5-hmC). Consequently, the TETs continue the oxidation of 5-hmC to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC) [ 19 , 20 ]. Among the TET family are the proteins Tet1, Tet2 and Tet3.…”
Aging is an inevitable outcome of life, characterized by a progressive decline in tissue and organ function. At a molecular level, it is marked by the gradual alterations of biomolecules. Indeed, important changes are observed on the DNA, as well as at a protein level, that are influenced by both genetic and environmental parameters. These molecular changes directly contribute to the development or progression of several human pathologies, including cancer, diabetes, osteoporosis, neurodegenerative disorders and others aging-related diseases. Additionally, they increase the risk of mortality. Therefore, deciphering the hallmarks of aging represents a possibility for identifying potential druggable targets to attenuate the aging process, and then the age-related comorbidities. Given the link between aging, genetic, and epigenetic alterations, and given the reversible nature of epigenetic mechanisms, the precisely understanding of these factors may provide a potential therapeutic approach for age-related decline and disease. In this review, we center on epigenetic regulatory mechanisms and their aging-associated changes, highlighting their inferences in age-associated diseases.
“…9 Both DNA methylation and DNA hydroxymethylation are highly expressed in the mammalian brain and have been shown to be involved in brain development, neuronal maintenance, cognition, and aging. 10 Figure 1. Epigenetic control of gene expression. Chemical modifications on the DNA and histones along with noncoding RNAs epigenetically regulate gene expression.…”
Section: Epigenetic Mechanismsmentioning
confidence: 99%
“…9 Both DNA methylation and DNA hydroxymethylation are highly expressed in the mammalian brain and have been shown to be involved in brain development, neuronal maintenance, cognition, and aging. 10 Furthermore, 5mC and 5hmC levels are known to be altered in both neurodegenerative diseases and acute brain injury, including stroke. 2…”
Accumulating evidence indicates a central role for epigenetic modifications in the progression of stroke pathology. These epigenetic mechanisms are involved in complex and dynamic processes that modulate post-stroke gene expression, cellular injury response, motor function, and cognitive ability. Despite decades of research, stroke continues to be classified as a leading cause of death and disability worldwide with limited clinical interventions. Thus, technological advances in the field of epigenetics may provide innovative targets to develop new stroke therapies. This review presents the evidence on the impact of epigenomic readers, writers, and erasers in both ischemic and hemorrhagic stroke pathophysiology. We specifically explore the role of DNA methylation, DNA hydroxymethylation, histone modifications, and epigenomic regulation by long non-coding RNAs in modulating gene expression and functional outcome after stroke. Furthermore, we highlight promising pharmacological approaches and biomarkers in relation to epigenetics for translational therapeutic applications.
“…A prominent and well understood example of epigenetic modification during development is the addition and removal of a methyl group at the C-5 position of the DNA cytosine ring by DNA methyltransferases and DNA demethylases dubbed writers and erasers, respectively. The writers of DNA methylation comprise the de novo DNA methyltransferases DNMT3A and DNMT3B and the maintenance methylase DNMT1, while active DNA demethylation is carried out by the ten-eleven translocation (TET) enzymes (TET1-3 in mammals) through oxidation of methylcytosine to hydroxymethylcytosine followed by a base excision repair pathway [ 5 ]. Eukaryotic DNA methylation is predominantly observed in the context of CpG dinucleotides in the genome and is observed at the promoters of virtually all housekeeping genes, developmentally regulated genes and genomic regulatory elements [ 6 , 7 ].…”
The epigenome controls all aspect of eukaryotic development as the packaging of DNA greatly affects gene expression. Epigenetic changes are reversible and do not affect the DNA sequence itself but rather control levels of gene expression. As a result, the science of epigenetics focuses on the physical configuration of chromatin in the proximity of gene promoters rather than on the mechanistic effects of gene sequences on transcription and translation. In the present review we discuss three prominent epigenetic modifications, DNA methylation, histone methylation/acetylation, and the effects of chromatin remodeling complexes. Specifically, we introduce changes to the methylated state of DNA through DNA methyltransferases and DNA demethylases, discuss the effects of histone tail modifications such as histone acetylation and methylation on gene expression and present the functions of major ATPase subunit containing chromatin remodeling complexes. We also introduce examples of how changes in these epigenetic factors affect early development in humans and mice. In summary, this review provides an overview over the most important epigenetic mechanisms and provides examples of the dramatic effects of epigenetic changes in early mammalian development.
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