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At least 19 recordsLinked to original sources
PubMed2005

Epigenetics and its implications for plant biology 2. The 'epigenetic epiphany': epigenetics, evolution and beyond.

SCOPE: In the second part of a two-part review, the ubiquity and universality of epigenetic systems is emphasized, and attention is drawn to the key roles they play, ranging from transducing environmental signals to altering gene expression, genomic architecture and defence. KEY ISSUES: The importance of transience versus heritability in epigenetic marks is examined, as are the potential for stable epigenetic marks to contribute to plant evolution, and the mechanisms generating novel epigenetic variation, such as stress and interspecific hybridization. FUTURE PROSPECTS: It is suggested that the ramifications of epigenetics in plant biology are immense, yet unappreciated. In contrast to the ease with which the DNA sequence can be studied, studying the complex patterns inherent in epigenetics poses many problems. Greater knowledge of patterns of epigenetic variation may be informative in taxonomy and systematics, as well as population biology and conservation.

Arabidopsis↗
PubMed2002

Epigenetic risks related to assisted reproductive technologies: risk analysis and epigenetic inheritance.

A broad spectrum of assisted reproductive technologies has become available for couples with fertility problems. Follow-up studies of children born as a result of assisted reproduction have shown that neonatal outcome and malformation rates are not different from those of the general population, except for a low birthweight and a slight increase in chromosomal abnormalities. The safety aspect of assisted reproduction at the epigenetic level has not been well studied. Epigenetics refers to phenomena where modifications of DNA methylation and/or chromatin structure underlie changes in gene expression and phenotype characteristics. This article intends to analyse epigenetic risks related to assisted reproduction on the basis of an overview of epigenetic reprogramming events in the gamete and early embryo. Two epigenetic modifications, methylation and imprinting, are considered in more detail. The interference of in-vitro embryo culture, immature sperm cells and nuclear transfer with epigenetic reprogramming is discussed, as well as the possibility of epigenetic inheritance.

Animals↗
PubMed2005

Epigenetics and its implications for plant biology. 1. The epigenetic network in plants.

BACKGROUND: Epigenetics has rapidly evolved in the past decade to form an exciting new branch of biology. In modern terms, 'epigenetics' studies molecular pathways regulating how the genes are packaged in the chromosome and expressed, with effects that are heritable between cell divisions and even across generations. CONTEXT: Epigenetic mechanisms often conflict with Mendelian models of genetics, and many components of the epigenetic systems in plants appeared anomalous. However, it is now clear that these systems govern how the entire genome operates and evolves. SCOPE: In the first part of a two-part review, how epigenetic systems in plants were elucidated is addressed. Also there is a discussion on how the different components of the epigenetic system--regulating DNA methylation, histones and their post-translational modification, and pathways recognizing aberrant transcripts--may work together.

Alleles↗
PubMed2004

Epigenetics in human disease and prospects for epigenetic therapy.

Epigenetic mechanisms, which involve DNA and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. The study of human disease has focused on genetic mechanisms, but disruption of the balance of epigenetic networks can cause several major pathologies, including cancer, syndromes involving chromosomal instabilities, and mental retardation. The development of new diagnostic tools might reveal other diseases that are caused by epigenetic alterations. Great potential lies in the development of 'epigenetic therapies'--several inhibitors of enzymes controlling epigenetic modifications, specifically DNA methyltransferases and histone deacetylases, have shown promising anti-tumorigenic effects for some malignancies.

DNA Methylation↗
PubMed2026

Epigenetic modulators in triple-negative breast cancer: epigenetic modifications and future treatment perspectives.

Triple Negative Breast Cancer (TNBC), an aggressive type of Breast Cancer (BC) characterized by the loss of expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2) protein. TNBC is quite heterogenous in nature with limited available therapeutic options due to the lack of defined molecular targets. Epigenetic abnormalities have been implicated in the onset, progression, immune escape, and resistance to treatment in TNBC. Important epigenetic modulations, include DNA methylation, histone lactylation, histone modifications, and chromatin remodeling. Global hypomethylation contributes to genomic instability, while promoter hypermethylation inhibits tumor suppressor genes, by dysregulating their expression, thereby promoting uncontrolled proliferation, EMT, metastasis, and immune evasion in TNBC. Targeting epigenetic modulators, have the potential to develop novel therapeutic interventions have been developed and being explored. These epidrugs have proven to be effective in preclinical and clinical trials when used in combination with chemotherapy, immunotherapy, or targeted therapy, reducing drug resistance and aberrant proliferation. Despite of the advancements, challenges like target specificity, precise biomarkers and treatment related toxicity are the major hurdles. The review comprehensively summarized the important epigenetic alterations as well as novel treatment strategies with potential clinical applications in TNBC.

Humans↗
PubMed2001

Epigenetic developmental mechanisms in plants: molecules and targets of plant epigenetic regulation.

Genetic approaches to understanding the role of epigenetic regulation of gene expression in plants and its mechanisms have revealed several new components. Rapidly accumulating information from other eukaryotes provides complementary knowledge with important implications for plant research. Comparison of epigenetic events across species is proving critical for defining the mechanisms and functions of epigenetic modification, including those specific to plants.

Chromatin↗
PubMed2006

Keeping up NF-kappaB appearances: epigenetic control of immunity or inflammation-triggered epigenetics.

Controlled expression of cytokine genes is an essential component of an immune response and is crucial for homeostasis. In order to generate an appropriate response to an infectious condition, the type of cytokine, as well as the cell type, dose range and the kinetics of its expression are of critical importance. The nuclear factor-kappaB (NF-kappaB) family of transcription factors has a crucial role in rapid responses to stress and pathogens (innate immunity), as well as in development and differentiation of immune cells (acquired immunity). Although quite a number of genes contain NF-kappaB-responsive elements in their regulatory regions, their expression pattern can significantly vary from both a kinetic and quantitative point of view, reflecting the impact of environmental and differentiative cues. At the transcription level, selectivity is conferred by the expression of specific NF-kappaB subunits and their respective posttranslational modifications, and by combinatorial interactions between NF-kappaB and other transcription factors and coactivators, that form specific enhanceosome complexes in association with particular promoters. These enhanceosome complexes represent another level of signaling integration, whereby the activities of multiple upstream pathways converge to impress a distinct pattern of gene expression upon the NF-kappaB-dependent transcriptional network. Today, several pieces of evidence suggest that the chromatin structure and epigenetic settings are the ultimate integration sites of both environmental and differentiative inputs, determining proper expression of each NF-kappaB-dependent gene. We will therefore discuss in this review the multilayered interplay of NF-kappaB signaling and epigenome dynamics, in achieving appropriate gene expression responses and transcriptional activity.

Animals↗
PubMed2003

Epigenetic risks related to assisted reproductive technologies: epigenetics, imprinting, ART and icebergs?

Recently, a series of case reports and small studies has suggested that births involving assisted reproductive technology (ART) may have an increased risk of imprinting disorders such as Beckwith-Wiedemann syndrome and Angelman syndrome. Herein, the significance and implications of these findings are discussed. It is speculated that, although such imprinting disorders may be shown to be only rare complications of ART, epigenetic errors might account for a much wider spectrum of ART-related complications than is recognized currently. Addressing these questions should be a priority for research on cohorts of ART children.

Angelman Syndrome↗
PubMed2025

A content analysis of health-related epigenetic information in YouTube videos.

PURPOSE: This study aimed to explore how health-related epigenetic concepts are depicted in YouTube videos, a widely accessed platform for informal science education. As epigenetics becomes increasingly relevant to medical therapeutics, it is essential to understand what information is being disseminated in the public sphere. METHODS: We conducted a content analysis of 296 YouTube videos about epigenetics that were under 10 minutes in length. We transcribed and analyzed the videos using an iteratively developed codebook and then categorized relevant codes as categories. RESULTS: We identified 7 categories: (1) defining epigenetics, (2) causes of epigenetic changes, (3) effects of epigenetic change, (4) epigenetic inheritability, (5) application of epigenetics, (6) personal control, and (7) epigenetic mysticism. Although the content about the molecular epigenetic mechanisms mostly aligned with the latest scientific findings, there were numerous unsubstantiated and exaggerated claims about effects of epigenetics on human health, especially disease outcomes. CONCLUSION: We identified several scientific concepts described on YouTube regarding epigenetics. Our findings also reveal what information about epigenetics is widely shared in the public sphere, helping to identify key misconceptions to address and guiding the development of strategies for accurate scientific communication.

Humans↗
PubMed2002

Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1.

The establishment and maintenance of mitotic and meiotic stable (epigenetic) transcription patterns is fundamental for cell determination and function. Epigenetic regulation of transcription is mediated by epigenetic activators and repressors, and may require the establishment, 'spreading' and maintenance of epigenetic signals. Although these signals remain unclear, it has been proposed that chromatin structure and consequently post-translational modification of histones may have an important role in epigenetic gene expression. Here we show that the epigenetic activator Ash1 (ref. 5) is a multi-catalytic histone methyl-transferase (HMTase) that methylates lysine residues 4 and 9 in H3 and 20 in H4. Transcriptional activation by Ash1 coincides with methylation of these three lysine residues at the promoter of Ash1 target genes. The methylation pattern placed by Ash1 may serve as a binding surface for a chromatin remodelling complex containing the epigenetic activator Brahma (Brm), an ATPase, and inhibits the interaction of epigenetic repressors with chromatin. Chromatin immunoprecipitation indicates that epigenetic activation of Ultrabithorax transcription in Drosophila coincides with trivalent methylation by Ash1 and recruitment of Brm. Thus, histone methylation by Ash1 may provide a specific signal for the establishment of epigenetic, active transcription patterns.

Animals↗
PubMed1998

Stepping into the same river twice: homologues as recurring attractors in epigenetic landscapes.

The reunification of embryology with evolutionary biology is impeded by the perception that a phylogenetic view of homology is incompatible with a developmental approach. This dichotomy disappears when developmental information is viewed not as pre-existing within the zygote but as being constructed during development. Developmental information can be depicted as the surface of an epigenetic landscape. An epigenetic landscape, in turn, can be viewed as a series of aligned energy landscapes that change shape and become more complex as development proceeds. In this view, individual valley bottoms are attractors in state space that tend to reappear reliably in successive generations. Phylogeny can therefore be conceptualized as a succession of epigenetic landscapes, and homologues can be identified as corresponding valleys that have reappeared reliably since their origin in a single ancestral population. Epigenetic homologues can be robust to phylogenetic changes in developmental mechanisms, precursors, and lower level characters. Although application of the epigenetic homology concept is complicated by the lack of explicit information about the topography of epigenetic landscapes, comparative biologists can learn to identify recurring ontogenetic patterns in a manner that is analogous to the identification of input patterns by attractor neural networks. The correspondence of epigenetic valleys is therefore not defined by any essential criteria but by their overlap in multidimensional state space. Whether corresponding valleys are homologous to each other must be determined by a phylogenetic analysis using cladistic methods. Among the general implications of epigenetic homology for comparative neurobiology is that the concept of 'field homology' should be used with caution when dealing with novel characters. A case study, applying an epigenetic perspective to understand the variation in monkey visual cortex observed after developmental perturbations, is presented in a final section to make the concept of epigenetic homology more concrete.

Biological Evolution↗
PubMed2006

Can the state of cancer chemotherapy resistance be reverted by epigenetic therapy?

BACKGROUND: Transcriptome analysis shows that the chemotherapy innate resistance state of tumors is characterized by: poorly dividing tumor cells; an increased DNA repair; an increased drug efflux potential by ABC-transporters; and a dysfunctional ECM. Because chemotherapy resistance involves multiple genes, epigenetic-mediated changes could be the main force responsible of this phenotype. Our hypothesis deals with the potential role of epigenetic therapy for affecting the chemotherapy resistant phenotype of malignant tumors. PRESENTATION OF THE HYPOTHESIS: Recent studies reveal the involvement of DNA methylation and histone modifications in the reprogramming of the genome of mammalian cells in cancer. In this sense, it can be hypothesized that epigenetic reprogramming can participate in the establishment of an epigenetic mark associated with the chemotherapy resistant phenotype. If this were correct, then it could be expected that agents targeting DNA methylation and histone deacetylation would by reverting the epigenetic mark induce a global expression profile that mirror the observed in untreated resistant cells. TESTING THE HYPOTHESIS: It is proposed to perform a detailed analysis using all the available databases where the gene expression of primary tumors was analyzed and data correlated with the therapeutic outcome to determine whether a transcriptome profiling of "resistance" is observed. Assuming an epigenetic programming determines at some level the intrinsic resistant phenotype, then a similar pattern of gene expression dictated by an epigenetic mark should also be found in cell acquiring drug resistance. If these expectations are meet, then it should be further investigated at the genomic level whether these phenotypes are associated to certain patterns of DNA methylation and chromatin modification. Once confirmed the existence of an epigenetic mark associated to either the intrinsic or acquired chemotherapy resistant phenotype, then a causal association should be investigated. These preclinical findings should also be tested in a clinical setting. IMPLICATIONS OF THE HYPOTHESIS: Our hypothesis on the ability of epigenetic therapy to revert the epigenetic changes leading to a transcritome profile that defines the resistant state will eventually be a more rational and effective way to treat malignant tumors.

Acetylation↗
PubMed2025

Stochastic epigenetic mutation profiles as biomarkers of clinical activity in juvenile idiopathic arthritis: a multi-omic machine learning approach for gene prioritization.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a rare autoimmune disease arising from a complex interplay between genetic and environmental factors. Epigenetic modifications such as DNA methylation (DNAm) have been described as potential mediators in gene-environment interactions, contributing to immune system dysregulation. Emerging evidence suggests that DNAm profiles also predict therapeutic responses in autoimmune diseases. This study aims to identify epigenetic biomarkers and epigenetic-driven gene expression changes associated with JIA clinical activity. METHODS: We reanalyzed a publicly available dataset of 44 JIA patients, with whole-genome DNAm and gene expression from CD4 + T cells measured at two points: at anti-TNF therapy withdrawal (T0) and eight months later (Tend). At Tend, 30 patients maintained inactive disease (ID) while 14 did not (NO ID). We investigated differences between ID and NO ID patients in the epigenetic mutation load and various epigenetic clocks through linear regression models, and prioritized genomic regions with significantly higher number of epimutations in NO ID patients through machine learning. RESULTS: We found a higher mutation load in NO ID than ID patients, both at T0 and at Tend, with the differences at Tend reaching statistical significance (p = 0.02). In contrast, we found no evidence of association between epigenetic clocks and JIA clinical activity. Using a multi-omic approach, we identified a List of candidate epigenetically-driven differentially expressed genes, 80 up-regulated and 77 down-regulated, in NO ID patients. Finally, comparing our candidate gene list with the Connectivity Map database, we identified new candidate potential therapeutic targets. Key findings were validated in independent datasets: DNAm profiles from CD4 + T cells (56 JIA patients, 57 controls) and transcriptomic data from PBMCs of JIA patients with active or inactive disease, confirming dysregulation of pathways such as TNF-α signaling via NF-kB and TGF-β signaling among others. CONCLUSIONS: We described a significant association of epigenetic mutations with JIA clinical activity, indicating that epigenetic changes might precede clinical symptoms and may serve as biomarkers for early disease monitoring. Further, our results shed light on biomolecular mechanisms of JIA, supporting the development of more effective treatments.

Humans↗
PubMed2005

[Epigenetics and cancer].

Epigenetics is defined as "the study of mitotically and/or meiotically heritable changes in gene expression that cannot be explained by changes in the DNA sequence". Setting up the epigenetic program is crucial for correct development and its stable inheritance throughout its lifespan is essential for the maintenance of the tissue- and cell-specific functions of the organism. For many years, the genetic causes of cancer have hold centre stage. However, the recent wealth of information about the molecular mechanisms which, by modulating the chromatin structure, can regulate gene expression has high-lighted the predominant role of epigenetic modifications in the initiation and progression of numerous pathologies, including cancer. The nucleosome is the major target of these epigenetic regulation mechanisms. They include a series of tightly interconnected steps which starting with the setting ("writing") of the epigenetic mark till its "reading" and interpretation will result in long-term gene regulation. The major epigenetic changes associated with tumorigenesis are aberrant DNA methylation of CpG islands located in the promoter region of tumor suppressor gene, global genomic hypomethylation and covalent modifications of histone N-terminal tails which are protruding out from the nucleosome core. In sharp contrast with genetic modifications, epigenetic modifications are highly dynamic and reversible. The characterization of specific inhibitors directed against some key epigenetic players has opened a new and promising therapeutic avenue, the epigenetic therapy, since some inhibitors are already used in clinical trials.

Animals↗
PubMed2005

Epigenetic reprogramming in mammals.

Epigenetic marking systems confer stability of gene expression during mammalian development. Genome-wide epigenetic reprogramming occurs at stages when developmental potency of cells changes. At fertilization, the paternal genome exchanges protamines for histones, undergoes DNA demethylation, and acquires histone modifications, whereas the maternal genome appears epigenetically more static. During preimplantation development, there is passive DNA demethylation and further reorganization of histone modifications. In blastocysts, embryonic and extraembryonic lineages first show different epigenetic marks. This epigenetic reprogramming is likely to be needed for totipotency, correct initiation of embryonic gene expression, and early lineage development in the embryo. Comparative work demonstrates reprogramming in all mammalian species analysed, but the extent and timing varies, consistent with notable differences between species during preimplantation development. Parental imprinting marks originate in sperm and oocytes and are generally protected from this genome-wide reprogramming. Early primordial germ cells possess imprinting marks similar to those of somatic cells. However, rapid DNA demethylation after midgestation erases these parental imprints, in preparation for sex-specific de novo methylation during gametogenesis. Aberrant reprogramming of somatic epigenetic marks after somatic cell nuclear transfer leads to epigenetic defects in cloned embryos and stem cells. Links between epigenetic marking systems appear to be developmentally regulated contributing to plasticity. A number of activities that confer epigenetic marks are firmly established, while for those that remove marks, particularly methylation, some interesting candidates have emerged recently which need thorough testing in vivo. A mechanistic understanding of reprogramming will be crucial for medical applications of stem cell technology.

Animals↗