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Results for “epigenetics”

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At least 1,081 records · Page 60Linked to original sources
PubMed2005

Shaping the human NK cell repertoire: an epigenetic glance at KIR gene regulation.

Human NK cells are equipped with arrays of inhibitory and stimulatory KIR receptors, many of them specific for HLA class I molecules on target cells. These NK receptors enable the recognition of virally infected as well as malignantly transformed target cells, which have downregulated the expression of single or multiple HLA class I products. KIR are expressed in clonally distributed ways leading to highly individualized but stable NK cell repertoires. Here, progress is reviewed toward understanding the molecular mechanisms that govern the unusual expression characteristics of KIR genes. Recent results suggest that DNA methylation plays a crucial role in shaping the KIR repertoire and underline the importance of epigenetic mechanisms as regulatory switches in the immune system.

DNA Methylation↗
PubMed2006

Epigenetic processes and cancer risk assessment.

The U.S. Environmental Protection Agency's Guidelines for Carcinogen Risk Assessment encourages the use of mechanistic data in the assessment of human cancer risk at low (environmental) exposure levels. The key events that define a particular mode of action for tumor formation have been concentrated to date more on mutational responses that are broadly the result of induced DNA damage and enhanced cell proliferation. While it is clear that these processes are important in terms of tumor induction, other modes that fall under the umbrella of epigenetic responses are increasingly being considered to play an important role in susceptibility to tumor induction by environmental chemicals and as significant modifiers of tumor responses. Alterations in gene expression, DNA repair, cell cycle control, genome stability and genome reprogramming could be the result of modification of DNA methylation and chromatin remodeling patterns as a consequence of exposure to environmental chemicals. These concepts are described and discussed.

Animals↗
PubMed2026

Genomic and epigenetic regulatory mechanisms in exercise-based rehabilitation processes: Cellular and tissue remodeling, microvascular adaptation, and circulating biomarkers.

While exercise-based rehabilitation is known to positively impact functionally related parameters, the role of genomic and epigenomic responses coordinated with cellular, extracellular matrix (ECM), mitochondrial, and microvascular adaptations remains insufficiently investigated. This narrative review summarizes mechanistic evidence linking exercise-associated mechanical, metabolic, hypoxia-redox, inflammatory, and hemodynamic stimuli with tissue remodeling and clinically relevant biomarkers. Current findings indicate that integrin-focal adhesion kinase (FAK) signaling and Hippo YAP/TAZ pathways contribute to mechanical signal transduction, cytoskeletal regulation, and gene expression, whereas metabolic adaptation, ATP homeostasis, and protein synthesis are regulated through AMPK-PGC-1α, SIRT1, and mTOR-dependent pathways. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and noncoding RNA regulation, further influence cell-specific responses in myofibers, satellite cells, fibro-adipogenic progenitors, endothelial cells, pericytes, and immune cells. In addition, VEGF-VEGFR2, eNOS-NO, and KLF2/KLF4 signaling, together with extracellular matrix turnover and inflammation resolution, contribute to tissue repair and microvascular adaptation during rehabilitation. Importantly, acute exercise-induced molecular responses should not be interpreted as direct evidence of sustained tissue adaptation. Circulating microRNAs, extracellular vesicles, cell-free DNA, collagen-related markers, and vascular proteins represent promising approaches for monitoring rehabilitation-related changes; however, their clinical translation remains limited by challenges related to tissue specificity, biomarker kinetics, analytical variability, and the need for standardized validation alongside structural and functional outcomes.

AMPK–PGC-1α signaling↗
PubMed2005

Mechanisms underlying epigenetic effects of early social experience: the role of neuropeptides and steroids.

In mammals the neonatal period is a time of significant social interaction. This is true even in solitary species as females spend a significant amount of time nursing and caring for their offspring. In social species interactions may also include the father, older siblings and extended family members. This period is a time of significant development, including organization of the central nervous system, and therefore a time when the degree and type of social interaction influences the development and expression of social behavior in adulthood. The purpose of this review is to examine the possible mechanisms for the epigenetic effects of early social experience on the subsequent expression of social behavior. We propose that social interactions during the neonatal period organize the subsequent expression of behavior by altering sensitivity to neuropeptides and steroids. Both neuropeptides (e.g. oxytocin and arginine vasopressin) and steroids (e.g. estrogen) regulate or influence the expression of behaviors such as affiliation, aggression, sociosexual behavior, parental behavior, and responses to stress. Therefore, changes in sensitivity to these hormones via reorganization of receptors or changes in hormone production and secretion are potentially powerful mechanisms through which early social experience can mold subsequent social behaviors.

Animals↗
PubMed2005

Early life genetic, epigenetic and environmental factors shaping emotionality in rodents.

Childhood trauma is known to increase risk for emotional disorders and addiction. However, little is currently understood about the neurodevelopmental basis of these effects, or how genetic and epigenetic factors interact with the environment to shape the systems subserving emotionality. In this review, we discuss the use of rodent models of early life emotional experience to study these issues in the laboratory and present some of our pertinent findings. In rats, postnatal maternal separation can produce lasting increases in emotional behavior and stressor-reactivity, together with alterations in various brain neurotransmitter systems implicated in emotionality, including corticotropin-releasing factor, serotonin, norepinephrine, and glutamate. Genetic differences between inbred mouse strains have been exploited to further study how maternal behavior affects emotional development using techniques such as cross-fostering and generation of inter-strain hybrids. Together with our own recent data, the findings of these studies demonstrate the pervasive influence of maternal and social environments during sensitive developmental periods and reveal how genetic factors determine how these early life experiences can shape brain and behavior throughout life.

Animals↗
PubMed2005

Stem cells: from epigenetics to microRNAs.

The complexity and cellular diversity of the adult brain arises from the proliferation and differentiation of a small number of stem cells. The intrinsic state of stem cells depends on their spatial and temporal history and affects their responsiveness to extrinsic signals from the microenvironment. Stem cell self-renewal and differentiation along neuronal and glial lineages are defined by the dynamic interplay between transcription, epigenetic control, and posttranscriptional regulators, including microRNAs, whose key role in stem cell biology is just emerging.

Animals↗
PubMed2004

The autonomous pathway: epigenetic and post-transcriptional gene regulation in the control of Arabidopsis flowering time.

Mechanisms that mediate the control of flowering time have been accessed through a molecular genetic approach in Arabidopsis. Flowering is regulated by different pathways and, in the past year, all of the known components of the so-called autonomous pathway have been identified. The autonomous pathway comprises a combination of factors involved in RNA processing and epigenetic regulation that downregulate the floral repressor, FLOWERING LOCUS C (FLC). However, components of the autonomous pathway are more widely conserved in plant species other than Arabidopsis than is FLC. Therefore, the broadest lessons we learn from dissecting the function of the autonomous pathway may be in revealing how precision in regulated gene expression is delivered.

AGAMOUS Protein, Arabidopsis↗
PubMed2005

Genomic imprinting in plants: the epigenetic version of an Oedipus complex.

Genomic imprinting is a mitotically stable epigenetic modification that results in the functional non-equivalency of both parental genomes following fertilization. In flowering plants, studies of parent-of-origin effects have mostly identified genes that are only transcribed from a maternally inherited allele. In Arabidopsis, the Polycomb group protein MEDEA regulates seed development through the expression of the MADS-box gene PHERES1. Activation of the maternal MEDEA allele requires the function of DEMETER, a plant DNA glycosylase that also controls the transcriptional activity of the maternally inherited allele of the late-flowering gene FWA. Current studies of parent-of-origin effects have mostly identified genes that are only transcribed from a maternally inherited allele. Our current understanding of parent-of-origin effects could represent a new form of an Oedipus complex in which flowering plants prefer to rely transcriptionally on their maternal rather than their paternal chromosomes to ensure normal initiation of seed development.

Gene Expression Regulation, Plant↗
PubMed2005

Arabidopsis epigenetics: when RNA meets chromatin.

Recent work in plants and other eukaryotes has uncovered a major role for RNA interference in silent chromatin formation. The heritability of the silent state through multiple cell division cycles and, in some instances, through meiosis is assured by epigenetic marks. In plants, transposable elements and transgenes provide striking examples of the stable inheritance of repressed states, and are characterized by dense DNA methylation and heterochromatin histone modifications. Arabidopsis is a useful higher eukaryotes model with which to explore the crossroads between silent chromatin and RNA interference both during development and in the genome-wide control of repeat elements.

Arabidopsis↗
PubMed2005

Epigenetic control of plant development by Polycomb-group proteins.

Recent genetic studies indicate that the plant Polycomb-group genes play much broader roles in development than was initially apparent from their single mutant phenotypes. At the mechanistic level, evidence is accumulating that their protein products act together in complexes that direct changes in histone methylation patterns. We discuss recent studies that give clues as to how these epigenetic changes are propagated through mitosis, how they are interpreted, and how they might be reset.

Gene Expression Regulation, Developmental↗
PubMed2006

Epigenetics and imprinting of the trophoblast -- a workshop report.

Genomic imprinting is a remarkable process that causes genes to be expressed or repressed depending on their parental-origin. Imprinted genes play important roles in prenatal growth and organ development. Postnatally, imprinted genes can contribute to the regulation of metabolic pathways and behaviour associated with the control of resources. One of the most important sites of imprinted gene action is the placenta. During this workshop at the 11th meeting of the International Federation of Placenta Associations/European Placenta Group held in Glasgow, a series of short talks were presented providing an overview of the evolution, function and mechanisms of imprinting in mammals with particular reference to the placenta. In addition, epigenetic control of trophoblast development and function were considered. This report summarises the contributions to the workshop.

Animals↗
PubMed2006

Epigenetic and proteolytic inactivation of 14-3-3sigma in breast and prostate cancers.

14-3-3sigma is an epithelial marker whose expression is induced by DNA damage through a p53-dependent pathway. 14-3-3sigma functions sequesters cyclin B1-CDC2 complexes outside the nucleus and thereby contributes to a G2 arrest. Down-regulation or lack of 14-3-3sigma is a frequent event in breast and prostate cancers. Epigenetic silencing by CpG methylation, p53 inactivation, and proteasome-dependent proteolysis leads to loss of 14-3-3sigma. Hypermethylation of the 14-3-3sigma gene is often observed in precancerous lesions and likely to be causally linked to the onset of cancer. Proteolytic inactivation of 14-3-3sigma has been recently found in breast and prostate cancers. In breast cancer, the estrogen-responsive E3 ubiquitin ligase Efp specifically targets 14-3-3sigma for degradation. The E2 ubiquitin conjugating enzyme UBC8 and Efp also mediates ISG15 modification of 14-3-3sigma. Detection of 14-3-3sigma inactivation on the protein or DNA methylation level may be used for cancer prognosis. Furthermore, 14-3-3sigma may be a potential therapeutic target in breast and prostate cancer.

14-3-3 Proteins↗
PubMed2006

Epigenetic silencing of 14-3-3sigma in cancer.

The 14-3-3sigma gene is a direct target of the p53 tumor suppressor and its product inhibits cell cycle progression. Recently, a proteomic analysis revealed that 14-3-3sigma regulates additional cellular processes relevant to carcinogenesis, as migration and MAP-kinase signalling. The expression of 14-3-3sigma is down-regulated by CpG methylation in several types of human cancer, among them prostate, lung, breast and several types of skin cancer. The epigenetic inactivation of 14-3-3sigma occurs at an early stage of tumor development and may allow evasion from senescence and promote genomic instability. In the future the detection of CpG methylation of 14-3-3sigma may be used for diagnostic and prognostic purposes.

14-3-3 Proteins↗
PubMed2005

Epigenetic control of B cell differentiation.

Gene expression, differentiation and the specialized function of various cell types are controlled epigenetically by post-translational histone modifications. These modifications establish a "histone code" that is recognized by various regulatory proteins, thereby creating a stable pattern of gene expression. The focus of this review is to discuss how the chromatin modifications regulate immunoglobulin gene rearrangement and B cell differentiation.

Animals↗
PubMed2006

Centromere formation: from epigenetics to self-assembly.

This review is part of the Chromosome segregation and Aneuploidy series that focuses on the importance of chromosome segregation mechanisms in maintaining genome stability. Centromeres are specialized chromosomal domains that serve as the foundation for the mitotic kinetochore, the interaction site between the chromosome and the mitotic spindle. The chromatin of centromeres is distinguished from other chromosomal loci by the unique incorporation of the centromeric histone H3 variant, centromere protein A. Here, we review the genetic and epigenetic factors that control the formation and maintenance of centromeric chromatin and propose a chromatin self-assembly model for organizing the higher-order structure of the centromere.

Animals↗
PubMed2006

Searching for ways out of the autism maze: genetic, epigenetic and environmental clues.

Our understanding of human disorders that affect higher cognitive functions has greatly advanced in recent decades, and over 20 genes associated with non-syndromic mental retardation have been identified during the past 15 years. However, proteins encoded by "cognition genes" have such diverse neurodevelopmental functions that delineating specific pathogenetic pathways still poses a tremendous challenge. In this review, we summarize genetic, epigenetic and environmental contributions to neurodevelopmental alterations that either cause or confer vulnerability to autism, a disease primarily affecting social cognition. Taken together, these results begin to provide a unifying view of complex pathogenetic pathways that are likely to lead to autism spectrum disorders through altered neurite morphology, synaptogenesis and cell migration. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Animals↗
PubMed2004

DNA methyltransferase inhibitors: old and new drugs for an epigenetic cancer therapy.

The pharmacological inhibition of DNA methyltransferases provides novel opportunities for the therapy of human cancers. Several Phase III trials of DNA methyltransferase inhibitors have been completed successfully, but the efficacy of these compounds appears to be compromised by their lack of specificity. To address this issue, much work has been focused on defining the functional characteristics of human DNA methyltransferases. This knowledge will be essential for the design of a new generation of pharmacological inhibitors that target epigenetic processes.

Animals↗
PubMed2004

Perturbation of epigenetic status by toxicants.

It is becoming increasingly apparent that toxicant-induced changes in epigenetic status, particularly DNA methylation patterns, may play a role in some mechanisms of toxicity. Here, we discuss briefly the evidence that alterations in DNA methylation accompany, and may even promote, carcinogenesis induced by non-genotoxic chemicals. We also address recent findings indicating that the availability of dietary methyl donors can modulate DNA methylation levels and precipitate adverse effects.

Animals↗