Quantitative DNA methylation analysis: the promise of high-throughput epigenomic diagnostic testing in human neoplastic disease.
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DNA↗
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Results for “epigenomics”
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Towards the human cancer epigenome: a first draft of histone modifications.
The disruption of genomic DNA methylation patterns was the first epigenetic abnormality to be described in human cancer. This imbalance involves the promoter CpG island hypermethylation of tumor-suppressor genes, causing transcriptional repression, and global genomic hypomethylation, leading to chromosomal instability and reactivation of endoparasitic sequences. The relationship between DNA methylation and histone modifications was initially described in the context of the inactivation of female X chromosomes and of the demonstration of strong interactions between the DNA methylation machinery and chromatin modifiers. The repression of tumor-suppressor genes by promoter hypermethylation was also found to be associated with a specific histone modification index. However, this jigsaw was missing a piece: a global view of how the histone modification landscape was distorted in cancer cells. We have recently discovered this piece of the puzzle, demonstrating that the association between DNA methylation and histone modification aberrations in cancer also occurs at the global level. In human and mouse tumors, histone H4 undergoes a loss of monoacetylated and trimethylated lysines 16 and 20, respectively. Most importantly, these alterations occur within the context of the repetitive DNA sequences that also become hypomethylated in transformed cells. The global alterations of histone acetylation status suggest novel pathways by which histone acetyltransferases (HATs), histone methyltransferases (HMTs), and histone deacetylases (HDACs) may play roles as tumor-suppressor genes or oncogenes. In this regard, we have shown how the generation of particular fusion proteins involving HATs in leukemias is associated with an erasure of the monoacetylated lysine 16-H4 marker, whilst the loss of trimethylation at lysine 20-H4 disrupts heterochromatic domains and may reduce the response to DNA damage of cancer cells.
Acetylation↗
Triple analysis of the cancer epigenome: an integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation.
We developed a novel microarray system to assess gene expression, DNA methylation, and histone acetylation in parallel, and to dissect the complex hierarchy of epigenetic changes in cancer. An integrated microarray panel consisting of 1507 short CpG island tags located at the 5'-end regions (including the first exons) was used to assess effects of epigenetic treatments on a human epithelial ovarian cancer cell line. Treatment with methylation (5-aza-2'-deoxycytidine) or deacetylation (trichostatin A) inhibitors alone resulted in up-regulation of 1.9 or 1.1% of the genes analyzed; however, the combined treatment resulted in synergistic reactivation of more genes (10.4%; P < 0.001 versus either treatment alone). On the basis of either primary or secondary responses to the treatments, genes were identified as methylation-dependent or -independent. Synergistic reactivation of the methylation-dependent genes by 5-aza-2'-deoxycytidine plus trichostatin A revealed a functional interaction between methylated promoters and deacetylated histones. Increased expression of some methylation-independent genes was associated with enhanced histone acetylation, but up-regulation of most of the genes identified using this technology was because of events downstream of the epigenetic cascade. We demonstrate proof of principle for using the triple microarray system in analyzing the dynamic relationship between transcription factors and promoter targets in cancer genomes.
Acetylation↗
Epigenomics: the new frontier.
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Genomics↗
[Nutritionnal epigenomics: consequences of unbalanced diets on epigenetics processes of programming during lifespan and between generations].
Epigenetic changes associated with DNA methylation and histone modifications leading to chromatin remodeling and regulation of gene expression underlie the developmental programming of obesity, type 2 diabetes, cardiovascular diseases and metabolic syndrome. This review focuses on converging data supporting the hypothesis that, in addition to "thrifty genotype" inheritance, individuals with obesity, type 2 diabetes, and metabolic syndrome (MetS) with an increased risk of cardiovascular diseases have suffered improper "epigenetic programming" during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their lifetime, that could even be transmitted to the next generation(s). We highlight the susceptibility of epigenetic mechanisms controlling gene expression to environmental influences due to their inherent malleability, emphasizing the participation of transposable elements and the potential role of imprinted genes during critical time windows in epigenetic programming, from the very beginning of development, throughout life. Increasing our understanding on epigenetic patterns significance and their role in development, evolution and adaptation and on small molecules (nutrients, drugs) that reverse epigenetic (in)activation should provide us with the means to "unlock" silenced (enhanced) genes, and to "convert" the obsolete human thrifty genotype into a "squandering" phenotype.
Adult↗
[Epigenome and cancer: new possibilities of cancer prevention and therapy?].
In recent years it became evident that epigenetic control of gene expression plays important role in the development of cancer. Epigenetic alterations occur throughout all stages of carcinogenesis, what makes them excellent targets for both chemoprevention and, at later stages, chemotherapy. Two changes integral to epigenetic transcriptional control are DNA methylation and covalent modifications of histone proteins. In cancer cells, genome-wide hypomethylation is accompanied by local DNA hypermethylation with unique patterns exhibited by each tumor type. Hypermethylation of promoter regions of classic tumor suppressor genes in human cancers is at least as common as mutation as a mechanism for their inactivation. The second major layer of epigenetic transcriptional control is modification of histone proteins, particularly their acetylation. These two ways of epigenetic control are integrally linked. In this review we summarize the current knowledge about epigenetic events related to cancer and discuss the possibility of using them as chemotherapy or chemoprevention targets.
Animals↗
[Nutritional epigenomics of metabolic syndrome].
The importance of epigenetic alterations has been acknowledged in cancer for about two decades by an increasing number of molecular oncologists who contributed to deciphering the epigenetic codes and machinery and opened the road for a new generation of drugs now in clinical trials. However, the relevance of epigenetics to common diseases such as metabolic syndrome and cardiovascular disease was less conspicuous. This review focuses on converging data supporting the hypothesis that, in addition to "thrifty genotype" inheritance, individuals with metabolic syndrome (MetS)--combining disturbances in glucose and insulin metabolism, excess of predominantly abdominally distributed weight, mild dyslipidemia and hypertension, with the subsequent development of obesity, type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD)--have suffered improper "epigenetic programing" during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their life-time. Moreover, as seen for obesity and T2D, MetS tends to appear earlier in childhood, to be more severe from generation to generation and to affect more pregnant women. Thus, in addition to maternal effects, MetS patients may display "transgenerational effects" via the incomplete erasure of epigenetic marks endured by their parents and grandparents. We highlight the susceptibility of epigenetic mechanisms controlling gene expression to environmental influences due to their inherent malleability, emphasizing the participation of transposable elements and the potential role of imprinted genes during critical time windows in epigenetic programming, from the very beginning of development throughout life. Increasing our understanding on epigenetic patterns significance and small molecules (nutrients, drugs) that reverse epigenetic (in) activation should provide us with the means to he obsolete human thrifty genotype into a "squandering" phenotype.
Animals↗
[Studying the SUMO modification pathway: from molecular structure to regulation of epigenome].
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Animals↗
[Genes and epigenomic variability].
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DNA↗
[The epigenomic variability of somatic cells].
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Animals↗
Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat.
Increased levels of pup licking/grooming and arched-back nursing by rat mothers over the first week of life alter the epigenome at a glucocorticoid receptor gene promoter in the hippocampus of the offspring. Differences in the DNA methylation pattern between the offspring of High and Low licking/grooming--arched-back mothers emerge over the first week of life, are reversed with cross-fostering, persist into adulthood and are associated with altered histone acetylation and transcription factor (NGFI-A) binding to the glucocorticoid receptor promoter. Central infusion of the adult offspring with the histone deacetylase inhibitor trichostatin A removes the previously defined epigenomic group differences in histone acetylation, DNA methylation, NGFI-A binding, glucocorticoid receptor expression, and hypothalamic-pituitary-adrenal responses to stress, thus suggesting a causal relation between the epigenomic state, glucocorticoid receptor expression and the effects of maternal care on stress responses in the offspring. These findings demonstrate that an epigenomic state of a gene can be established through a behavioral mode of programming and that in spite of the inherent stability of this epigenomic mark, it is dynamic and potentially reversible.
Animals↗
[Epigenetics of the sperm cell].
In addition to genetic information, the spermatozoon carries another type of information, named epigenetic, which is not associated with variations of the DNA sequence. In somatic cells, it is now generally admitted that epigenetic information is not only regulated by DNA methylation but also involves modifications of the genome structure, or epigenome. During male germ cell maturation, the epigenome is globally re-organized, since most histones, which are associated to DNA in somatic cells, are removed and replaced by sperm specific nuclear proteins, the protamines, responsible for the tight compaction of the sperm DNA. However, a small proportion of histones, and probably other proteins, are retained within the sperm nucleus, and the structure of the sperm genome is actually heterogeneous. This heterogeneity of the sperm epigenome could support an epigenetic information, transmitted to the embryo, which could be crucial for its development. Although it is nowadays possible to appreciate the global structure of the sperm genome, the precise constitution of the sperm epigenome remains unknown. In particular, very recent data suggest that specific regions of the genome could be associated with particular proteins and define specific structures. This structural partitioning of the sperm genome could convey important epigenetic information, crucial for the embryo development.
DNA↗
Constructing epigenetic regulatory landscapes of plant lncRNAs-an exploration utilizing the novel specialized platform PERlncDB.
Long non-coding RNAs (lncRNAs), once overlooked as transcriptional byproducts, are now recognized for their crucial roles in plant growth, development, and stress responses, with increasing focus on their epigenetic regulation. However, studies investigating epigenomic signals to explore the functions of lncRNAs in plants remain relatively limited. This study collected a comprehensive dataset of over 160 000 high-quality lncRNAs from 19 representative plant species and integrated 6715 ChIP-seq, BS-seq, and RNA-seq datasets to analyze epigenomic patterns at lncRNA loci. Results showed elevated DNA methylation in lncRNA regions. The highest levels occurred in transposable element-associated lncRNAs. Additionally, activating histone modifications at lncRNA loci showed tissue specificity, with epigenetic preferences differed from those at protein-coding gene (PCG) loci. Differential site analysis in epigenetic mutants further highlighted the selective regulation of lncRNA loci by specific epigenetic factors. To facilitate research, we developed PERlncDB, a platform that provides species-specific lncRNA browsing, epigenetic annotation, cross-species conservation analysis, and visualization of epigenomic landscapes. Case studies on MARS and LINC-AP2 emphasized the platform's utility. Conserved epigenetic mechanisms regulating lncRNAs across species, exemplified by a syntenic conserved MET1-regulated lncRNA pair in Arabidopsis and tomato, suggested the stability of regulatory mechanisms underlying lncRNA functions. This work provides critical insights and resources for understanding plant lncRNA epigenetic regulation.
RNA, Long Noncoding↗
ChIP-Rx: Arabidopsis Chromatin Profiling Using Quantitative ChIP-Seq.
Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) is widely used to probe the chromatin landscape of transcription factors, chromatin components, and associated proteins. Conventional ChIP normalization procedures robustly allow estimating differences in local enrichment across genomic regions. Yet, inter-sample comparisons can be biased by technical variability and biological differences. This is notably the case when samples display large differences in the abundance of the target protein or its enrichment at chromatin. For example, epigenome defects are improperly detected or quantified upon large-effect genetic or chemical inhibition of chromatin modifiers. To circumvent these caveats and robustly determine biological variations while minimizing technical variability, ChIP adaptations using an external reference have flourished. Here, we describe a step-by-step protocol employing a reference exogenous chromatin (ChIP-Rx) that allows absolute comparisons of epigenome variations in Arabidopsis samples displaying drastic differences in chromatin mark abundance. In contrast to the originally published ChIP-Rx approach, which assumes that exogenous spike-in references are constant across samples, the method detailed here involves the sequencing of each input sample to account for technical variability in initial reference chromatin contents. We also report a detailed computational workflow with an accompanying Github resource to help in calculating spike-in normalization factors, applying them to normalize epigenome tracks, and performing spike-in normalized inter-sample differential analyses. We propose two ways of computing the spike-in factor: a classically used method based on raw counts and a noise-corrected method using peak detection on the exogenous genome.
Arabidopsis↗
Osteoarthritis Year in Review 2026: Genetics, genomics and epigenetics.
OBJECTIVE: The purpose of this narrative review is to highlight advances made over the past 12 months in the field of osteoarthritis (OA) genetics, genomics and epigenomics, with a particular focus on the interpretation of OA risk loci through functional genomic and regulatory approaches. DESIGN: PubMed and Europe PMC were searched to identify studies relevant to OA genetics, genomics and epigenomics published between 1st March 2025 and 30th April 2026. Searches used combinations of terms relating to genetics, genomics, epigenomics, functional genomics, molecular quantitative trait loci, chromatin accessibility and enhancer biology. Studies were limited to human subjects and English-language publications, with additional articles identified through citation screening and expert knowledge of the field. RESULTS: Over the past year, the field has continued to transition from large-scale locus discovery towards biological interpretation of OA genetic risk. Major advances included the largest OA genome-wide association study to date, further development of polygenic risk score approaches, and increasing integration of molecular quantitative trait loci, chromatin accessibility, and enhancer biology datasets to prioritise effector genes and elucidate regulatory mechanisms. Several studies highlighted the highly context-dependent nature of OA genetic risk mechanisms, demonstrating that distinct tissues, cell types, and regulatory layers can identify different candidate effector genes at the same locus. Additional developments included increasing application of singlecell and multi-omic technologies to study OA-relevant tissues. CONCLUSION: Recent advances in OA genetics have shifted the field from locus discovery towards mechanistic interpretation. Emerging evidence demonstrates that the biological consequences of genetic variation are highly dependent upon tissue, cell state and disease context, with different functional genomic approaches often prioritising distinct candidate genes and regulatory mechanisms at the same susceptibility locus. Together, these findings suggest that OA risk loci should increasingly be viewed as dynamic regulatory systems rather than simple variant-to-gene relationships, providing a framework for future studies aimed at resolving causal mechanisms, defining disease endotypes, and identifying therapeutic targets.
Genetics↗
Integrative WGBS and ATAC-seq profiling reveals epigenetic and chromatin accessibility signatures associated with clutch length in goose ovaries.
Clutch length is an important reproductive trait in geese, but its epigenetic basis remains poorly characterized. Daily egg production was recorded for 280 individually housed Zi geese, and clutch-related indices were calculated as described in our previous study. Based on these records, six geese with contrasting clutch-length phenotypes were selected and assigned to the long-clutch (LC) and short-clutch (SC) groups. Ovarian tissues from three geese per group were subjected to whole-genome bisulfite sequencing (WGBS) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) to identify candidate epigenetic signatures associated with clutch length. WGBS identified 630,909 differentially methylated regions (DMRs), whereas ATAC-seq identified 902 differentially accessible regions (DARs). Integrated analysis revealed distinct patterns of ovarian DNA methylation and chromatin accessibility between the two groups, suggesting that clutch length variation may be accompanied by epigenomic differences in ovarian tissue. Genes associated with DMRs and/or DARs were enriched in biological processes related to granulosa cell differentiation and endocrine competence, follicular fate regulation, and periovulatory cytoskeletal and signaling remodeling. RERE was prioritized as a candidate locus because it was supported by changes in both DNA methylation and chromatin accessibility, whereas FOXL2, STAR, BAK1, FGF17, PRSS35, ACTR3, and AXIN1 were supported mainly by evidence from a single omics layer. RT-qPCR analysis of selected genes showed expression trends broadly consistent with the corresponding epigenomic differences, providing additional supportive evidence for these candidate associations. Collectively, this study provides an exploratory ovarian epigenomic resource and identifies candidate epigenetic signatures, genes, and biological processes associated with clutch length variation in geese.
DNA methylation↗
Epigenetic gene regulation: linking early developmental environment to adult disease.
Traditional studies on the combined effects of genetics and the environment on individual variation in disease susceptibility primarily focus on single nucleotide polymorphisms that influence toxicant uptake and metabolism. A growing body of evidence, however, suggests that epigenetic mechanisms of gene regulation, such as DNA methylation and chromatin modification, are also influenced by the environment, and play an important role in the fetal basis of adult disease susceptibility. Studying the influence of early environmental exposures on metastable epialleles and imprinted genes offers insight into the mechanisms affecting the fetal epigenome and subsequent adult disease susceptibility. In this review, we introduce the reader to the field of environmental epigenomics, provide information on the important epigenetic control mechanisms and epigenetic phenomena in mammals, and summarize the current body of literature on nutritional and environmental influences affecting the epigenome.
Animals↗
Epigenetic programming by maternal behavior.
Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.
Acetylation↗