'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Fri, 25 Apr 2025 00:53:05 EDT Fri, 25 Apr 2025 00:53:05 EDT jirtle@radonc.duke.edu james001@jirtle.com Congenital Hyperinsulinism and Novel KDM6A Duplications -Resolving Pathogenicity With Genome and Epigenetic Analyses. Männistö JME, Hopkins JJ, Hewat TI, Nasser F, Burrage J, Dastamani A, Mirante A, Murphy N, Rzasa J, Kerkhof J, Relator R, Johnson MB, Laver TW, Weymouth L, Houghton JAL, Wakeling MN, Sadikovic B, Dempster EL, Flanagan SE
J Clin Endocrinol Metab (Apr 2025)

Hyperinsulinemic hypoglycemia (HI) can be the presenting feature of Kabuki syndrome (KS), which is caused by loss-of-function variants in KMT2D or KDM6A. As these genes play a critical role in maintaining methylation status in chromatin, individuals with pathogenic variants have a disease-specific epigenomic profile-an episignature.]]> Wed, 31 Dec 1969 19:00:00 EST Applying blood-derived epigenetic algorithms to saliva: cross-tissue similarity of DNA-methylation indices of aging, physiology, and cognition. Zarandooz S, Raffington L
Clin Epigenetics (Apr 2025)

Epigenetic algorithms of aging, health, and cognition, based on DNA-methylation (DNAm) patterns, are prominent tools for measuring biological age and have been linked to age-related diseases, cognitive decline, and mortality. While most of these methylation profile scores (MPSs) are developed in blood tissue, there is growing interest in using less invasive tissues like saliva. The aim of the current study is to probe the cross-tissue intraclass correlation coefficients (ICCs) of MPSs developed in blood applied to saliva DNAm from the same people. While our primary focus is on MPSs that were previously found to be robustly correlated with social determinants of health, including second- and third-generation clocks and MPSs of physiology and cognition, we also report ICC values for first-generation clocks to enable comparison across metrics. We pooled three publicly available datasets that had both saliva and blood DNAm from the same individuals (total n = 107, aged 5-74 years), corrected MPSs for cell composition within each tissue, and computed the cross-tissue ICCs.]]> Wed, 31 Dec 1969 19:00:00 EST Cardiometabolic disease management: influences from epigenetics. Atzemian N, Mohammed S, Di Venanzio L, Gorica E, Costantino S, Ruschitzka F, Paneni F
Epigenomics (May 2025)

Epigenomics is a rapidly emerging field that has gathered significant attention as a "non-genetic determinant" implicated in the manifestation of non-communicable diseases. Exploring epigenetic modifications provides novel insights into the management of cardiometabolic disease (CMD). Epigenetics signatures are influenced by environmental stressors such as air pollution, toxins, and urban noises as well as by established cardiovascular risk factors including smoking, sedentary lifestyle, obesity, and diabetes. Understanding how epigenetic alterations lead to CMD as well as inter-individual differences in epigenetic makeup could unveil new molecular targets and new epi-drugs to be employed for precision medicine approaches in the growing population of patients with cardiometabolic disease to reduce cardiovascular risk. Herein, we provide an overview of the latest advancements in epigenetic mechanisms implicated in CMD and possible therapeutic opportunities.]]> Wed, 31 Dec 1969 19:00:00 EST Mom genes and dad genes: genomic imprinting in the regulation of social behaviors. O'Leary EM, Bonthuis PJ
Epigenomics (Apr 2025)

Genomic imprinting is an epigenetic phenomenon in mammals that affects brain development and behavior. Imprinting involves the regulation of allelic expression for some genes in offspring that depends on whether alleles are inherited from mothers compared to fathers, and is thought to provide parental control over offspring social behavior phenotypes. Imprinted gene expression is prevalent in the mammalian brain, and human imprinted gene mutations are associated with neurodevelopmental disorders and neurodivergent social behavior in Prader-Willi Syndrome, Angelman Syndrome, and autism. Here, we provide a review of the evidence that imprinted genes influence social behaviors across major neurodevelopmental stages in humans and mouse animal models that include parent-infant interactions, juvenile sociability, and adult aggression, dominance, and sexual behavior.]]> Wed, 31 Dec 1969 19:00:00 EST Mechanisms of Impaired Wound Healing in Type 2 Diabetes: The Role of Epigenetic Factors. Bauer TM, Moon JY, Shadiow J, Buckley SD, Gallagher KA
Arterioscler Thromb Vasc Biol (May 2025)

Despite decades of research, impaired extremity wound healing in type 2 diabetes remains a significant driver of patient morbidity, mortality, and health care costs. Advances in surgical and medical therapies, including the advent of endovascular interventions for peripheral artery disease and topical therapies developed to promote wound healing, have not reduced the frequency of lower leg amputations for nonhealing wounds in type 2 diabetes. This brief report is aimed at reviewing the roles of various cell types in tissue repair and summarizing the known dysfunctions of these cell types in diabetic foot ulcers. Recent advances in our understanding of the epigenetic regulation in immune cells identified to be altered in type 2 diabetes are summarized, and particular attention is paid to the developing research defining the epigenetic regulation of structural cells, including keratinocytes, fibroblasts, and endothelial cells. Gaps in knowledge are highlighted, and potential future directions are suggested based on the current state of the field.]]> Wed, 31 Dec 1969 19:00:00 EST Unified molecular approach for spatial epigenome, transcriptome, and cell lineages. Huang YH, Belk JA, Zhang R, Weiser NE, Chiang Z, Jones MG, Mischel PS, Buenrostro JD, Chang HY
Proc Natl Acad Sci U S A (Apr 2025)

Spatial epigenomics and multiomics can provide fine-grained insights into cellular states but their widespread adoption is limited by the requirement for bespoke slides and capture chemistries for each data modality. Here, we present SPatial assay for Accessible chromatin, Cell lineages, and gene Expression with sequencing (SPACE-seq), a method that utilizes polyadenine-tailed epigenomic libraries to enable facile spatial multiomics using standard whole transcriptome reagents. Applying SPACE-seq to a human glioblastoma specimen, we reveal the state of the tumor microenvironment, extrachromosomal DNA copy numbers, and identify putative mitochondrial DNA variants.]]> Wed, 31 Dec 1969 19:00:00 EST Omics technologies as powerful approaches to unravel colorectal cancer complexity and improve its management. Fatfat Z, Hussein M, Fatfat M, Gali-Muhtasib H
Mol Cells (May 2025)

Colorectal cancer (CRC) continues to rank among the deadliest and most prevalent cancers worldwide, necessitating an innovative and comprehensive approach that addresses this serious health challenge at various stages, from screening and diagnosis to treatment and prognosis. As CRC research progresses, the adoption of an omics-centered approach holds transformative potential to revolutionize the management of this disease. Advances in omics technologies encompassing genomics, transcriptomics, proteomics, metabolomics, and epigenomics allow to unravel the oncogenic alterations at these levels, elucidating the intricacies and the heterogeneous nature of CRC. By providing a comprehensive molecular landscape of CRC, omics technologies enable the discovery of potential biomarkers for early non-invasive detection of CRC, definition of CRC subtypes, prediction of its staging, prognosis, and overall survival of CRC patients. They also allow the identification of potential therapeutic targets, prediction of drug response, tracking treatment efficacy, detection of residual disease and cancer relapse, and deciphering the mechanisms of drug resistance. Moreover, they allow the distinction of non-metastatic CRC patients from metastatic ones as well as the stratification of metastatic risk. Importantly, omics technologies open up new opportunities to establish molecular-based criteria to guide the selection of effective treatment paving the way for the personalization of therapy for CRC patients. This review consolidates current knowledge on the omics-based preclinical discoveries in CRC research emphasizing the significant potential of these technologies to improve CRC screening, diagnosis, and prognosis and promote the implementation of personalized medicine to ultimately reduce CRC prevalence and mortality.]]> Wed, 31 Dec 1969 19:00:00 EST Enhancing the neural differentiation capabilities of genetically asymmetric mouse F1 hybrid embryonic stem cell lines. Saito A, Kato H, Kiyosawa H
Exp Anim (Apr 2025)

Allele-specific, monoallelic expression in diploid organisms represents an extreme case of allelic imbalance resulting from incompatibility between cis- and trans-elements. Due to haploinsufficiency, such monoallelic expression can lead to sporadic genetic diseases. In mice, allelic imbalances can be introduced into F1 offspring from inbred strains. Previously, we established F1 hybrid embryonic stem (ES) cell lines derived from four different mouse strains, each belonging to a different subspecies with substantial genetic polymorphisms. In this study, we investigated the neural differentiation capacity of the established ES cell lines. By introducing different culture conditions, which kept the ES cells undifferentiated under various pluripotencies, we succeeded in differentiating the majority of ES cell lines (eight out of eleven) with our default neural differentiation paradigm. Still, three lines exhibited insufficient differentiation despite combining culture conditions promoting undifferentiated as well as differentiated status. In addition, Ube3a imprinting was seen in two lines. Our findings contribute to the methodological understanding of mouse ES cell pluripotency and lead to the practical utility of F1 hybrid ES cells as a model for studying phenotypes resulting from gene locus interactions.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic ageing clocks: statistical methods and emerging computational challenges. Teschendorff AE, Horvath S
Nat Rev Genet (May 2025)

Over the past decade, epigenetic clocks have emerged as powerful machine learning tools, not only to estimate chronological and biological age but also to assess the efficacy of anti-ageing, cellular rejuvenation and disease-preventive interventions. However, many computational and statistical challenges remain that limit our understanding, interpretation and application of epigenetic clocks. Here, we review these computational challenges, focusing on interpretation, cell-type heterogeneity and emerging single-cell methods, aiming to provide guidelines for the rigorous construction of interpretable epigenetic clocks at cell-type and single-cell resolution.]]> Wed, 31 Dec 1969 19:00:00 EST Host-microbe multi-omics and succinotype profiling have prognostic value for future relapse in patients with inflammatory bowel disease. O'Sullivan J, Patel S, Leventhal GE, Fitzgerald RS, Laserna-Mendieta EJ, Huseyin CE, Konstantinidou N, Rutherford E, Lavelle A, Dabbagh K, DeSantis TZ, Shanahan F, Temko A, Iwai S, Claesson MJ
Gut Microbes (Dec 2025)

Crohn's disease (CD) and ulcerative colitis (UC) are chronic relapsing inflammatory bowel disorders (IBD), the pathogenesis of which is uncertain but includes genetic susceptibility factors, immune-mediated tissue injury and environmental influences, most of which appear to act via the gut microbiome. We hypothesized that host-microbe alterations could be used to prognostically stratify patients experiencing relapses up to four years after endoscopy. We therefore examined multiple omics data, including published and new datasets, generated from paired inflamed and non-inflamed mucosal biopsies from 142 patients with IBD (54 CD; 88 UC) and from 34 control (non-diseased) biopsies. The relapse-predictive potential of 16S rRNA gene and transcript amplicons (standing and active microbiota) were investigated along with host transcriptomics, epigenomics and genetics. While standard single-omics analysis could not distinguish between patients who relapsed and those that remained in remission within four years of colonoscopy, we did find an association between the number of flares and a patient's succinotype. Our multi-omics machine learning approach was also able to predict relapse when combining features from the microbiome and human host. Therefore multi-omics, rather than single omics, better predicts relapse within 4 years of colonoscopy, while a patient's succinotype is associated with a higher frequency of relapses.]]> Wed, 31 Dec 1969 19:00:00 EST On integrative analysis of multi-level gene expression data in Kidney cancer subgrouping. Jeyananthan P, W P N M, S M R
Urologia (May 2025)

Kidney cancer is one of the most dangerous cancer mainly targeting men. In 2020, around 430, 000 people were diagnosed with this disease worldwide. It can be divided into three prime subgroups such as kidney renal cell carcinoma (KIRC), kidney renal papilliary cell carcinoma (KIRP) and kidney chromophobe (KICH). Correct identification of these subgroups on time is crucial for the initiation and determination of proper treatment. On-time identification of this disease and its subgroup can help both the clinicians and patients to improve the situation. Hence, this study checks the possibility of using multi-omics data in the kidney cancer subgrouping, whether integrating multiple omics data will increase the subgrouping accuracy or not. Four different molecular data such as genomics, proteomics, epigenomics and miRNA from The Cancer Genome Atlas (TCGA) are used in this study. As the data is in a very high dimension world, this study starts with selecting the relevant features of the study using Pearson's correlation coefficient. Those selected features are used with three different classification algorithms such as k-nearest neighbor (KNN), supporting vector machines (SVMs) and random forest. Performances are compared to see whether the integration of multi-omics data can improve the accuracy of kidney cancer subgrouping. This study shows that integration of multi-omics data can improve the performance of the kidney cancer subgrouping. The highest performance (accuracy value of 0.98±0.03) is gained by top 400 features selected from integrated multi-omics data, with support vector machines.]]> Wed, 31 Dec 1969 19:00:00 EST Weighted 2D-kernel density estimations provide a new probabilistic measure for epigenetic age. Perez-Correa JF, Stiehl T, Marioni RE, Corley J, Cox SR, Costa IG, Wagner W
Genome Biol (Apr 2025)

Epigenetic aging signatures provide insights into human aging, but traditional clocks rely on linear regression of DNA methylation levels, assuming linear trajectories. This study explores a non-parametric approach using 2D-kernel density estimation to determine epigenetic age. Our weighted model achieves similar predictive accuracy as conventional clocks and provides a variation score reflecting the inherent variability of age-related epigenetic changes within samples. This score is significantly increased in various diseases and associated with mortality risk in the Lothian Birth Cohort 1921. Thus, weighted 2D-kernel density estimation facilitates accurate epigenetic age predictions and offers an additional variable for biological age estimation.]]> Wed, 31 Dec 1969 19:00:00 EST Emerging Techniques in Spatial Multiomics: Fundamental Principles and Applications to Dermatology. Jia BB, Sun BK, Lee EY, Ren B
J Invest Dermatol (May 2025)

Molecular pathology, such as high-throughput genomic and proteomic profiling, identifies precise disease targets from biopsies but require tissue dissociation, losing valuable histologic and spatial context. Emerging spatial multi-omic technologies now enable multiplexed visualization of genomic, proteomic, and epigenomic targets within a single tissue slice, eliminating the need for labeling multiple adjacent slices. Although early work focused on RNA (spatial transcriptomics), spatial technologies can now concurrently capture DNA, genome accessibility, histone modifications, and proteins with spatially-resolved single-cell resolution. This review outlines the principles, advantages, limitations, and potential for spatial technologies to advance dermatologic research. By jointly profiling multiple molecular channels, spatial multiomics enables novel studies of copy number variations, clonal heterogeneity, and enhancer dysregulation, replete with spatial context, illuminating the skin's complex heterogeneity.]]> Wed, 31 Dec 1969 19:00:00 EST Bidirectional disruption of transcripts causes broad methylation defects in pseudohypoparathyroidism type 1B. Iwasaki Y, Reyes M, Ryabets-Lienhard A, Gales B, Linglart A, Miller DE, Salusky IB, Bastepe M, Jüppner H
Proc Natl Acad Sci U S A (Apr 2025)

Pseudohypoparathyroidism type 1B (PHP1B) is a multihormone resistance disorder caused by aberrant methylation. Characteristic epigenetic changes at differentially methylated regions (DMRs), i.e., NESP, AS1, AS2, XL, and A/B, are associated with specific structural defects in different autosomal dominant PHP1B (AD-PHP1B) subtypes. However, mechanisms underlying abnormal methylation remain incompletely defined, largely because viable PHP1B mouse models are lacking. Using lymphoblastoid cells and induced pluripotent stem cells, we show that various methylation patterns in PHP1B reflect differential disruption of sense and antisense transcripts. In cases with broad methylation changes, loss of the maternal, sense-transcribed exon H/AS region impairs methylation of the AS1 DMR, which results in biallelic expression of an antisense transcript, , and NESP hypermethylation. In contrast, cases with normal AS1 methylation, including deletions, show monoallelic expression and normal NESP methylation. The roles of these transcripts were confirmed by a retrotransposon in intron 1, identified in an AD-PHP1B family. This insertion impaired exon H/AS transcription when located on the maternal allele, thus preventing the complete establishment of methylation at all maternal DMRs, leading to biallelic transcription. However, maternal transcription was profoundly attenuated, thus allowing only a small gain-of-methylation at NESP. Likewise, on the paternal allele, the retrotransposon attenuated transcription, thus preventing complete NESP methylation. Our findings support a model of bidirectional transcription-mediated regulation of methylation at DMRs and will help to refine systematic approaches for establishing molecular defects underlying different PHP1B subtypes.]]> Wed, 31 Dec 1969 19:00:00 EST Developmental epigenomic effects of maternal financial problems. Holuka C, Menta G, Caro JC, Vögele C, D'Ambrosio C, Turner JD
Dev Psychopathol (May 2025)

Early-life adversity as neglect or low socioeconomic status is associated with negative physical/mental health outcomes and plays an important role in health trajectories through life. The early-life environment has been shown to be encoded as changes in epigenetic markers that are retained for many years.We investigated the effect of maternal major financial problems (MFP) and material deprivation (MD) on their children's epigenome in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Epigenetic aging, measured with epigenetic clocks, was weakly accelerated with increased MFP. In subsequent EWAS, MFP, and MD showed strong, independent programing effects on children's genomes. MFP in the period from birth to age seven was associated with genome-wide epigenetic modifications on children's genome visible at age 7 and partially remaining at age 15.These results support the hypothesis that physiological processes at least partially explain associations between early-life adversity and health problems later in life. Both maternal stressors (MFP/MD) had similar effects on biological pathways, providing preliminary evidence for the mechanisms underlying the effects of low socioeconomic status in early life and disease outcomes later in life. Understanding these associations is essential to explain disease susceptibility, overall life trajectories and the transition from health to disease.]]> Wed, 31 Dec 1969 19:00:00 EST Strengthening Rigor and Reproducibility in Epigenome-Wide Association Studies of Social Exposures and Brain-Based Health Outcomes. McKenna BG, Lussier AA, Suderman MJ, Walton E, Simpkin AJ, Hüls A, Dunn EC
Curr Environ Health Rep (Apr 2025)

Studies examining the effects of social factors on the epigenome have proliferated over the last two decades. Social epigenetics research to date has broadly demonstrated that social factors spanning childhood adversity, to neighborhood disadvantage, educational attainment, and economic instability are associated with alterations to DNA methylation that may have a functional impact on health. These relationships are particularly relevant to brain-based health outcomes such as psychiatric disorders, which are strongly influenced by social exposures and are also the leading cause of disability worldwide. However, social epigenetics studies are limited by the many challenges faced by both epigenome-wide association studies (EWAS) and the study of social factors.]]> Wed, 31 Dec 1969 19:00:00 EST Exploring omics solutions to reduce micro/nanoplastic toxicity in plants: A comprehensive overview. Arif SM, Khan I, Saeed M, Chaudhari SK, Ghorbanpour M, Hasan M, Mustafa G
Sci Total Environ (Apr 2025)

The proliferation of plastic waste, particularly in the form of microplastics (MPs) and nanoplastics (NPs), has emerged as a significant environmental challenge with profound implications for agricultural ecosystems. These pervasive pollutants accumulate in soil, altering its physicochemical properties and disrupting microbial communities. MPs/NPs can infiltrate plant systems, leading to oxidative stress and cytotoxic effects, which in turn compromise essential physiological functions such as water uptake, nutrient absorption, and photosynthesis. This situation threatens crop yield and health, while also posing risks to human health and food security through potential accumulation in the food chain. Despite increasing awareness of this issue, substantial gaps still remain in our understanding of the physiological and molecular mechanisms that govern plant responses to MP/NP stress. This review employs integrative omics techniques including genomics, transcriptomics, proteomics, metabolomics, and epigenomics to elucidate these responses. High-throughput methodologies have revealed significant genetic and metabolic alterations that enable plants to mitigate the toxicity associated with MPs/NPs. The findings indicate a reconfiguration of metabolic pathways aimed at maintaining cellular homeostasis, activation of antioxidant mechanisms, and modulation of gene expression related to stress responses. Additionally, epigenetic modifications suggest that plants adapt to prolonged plastics exposure, highlighting unexplored avenues for targeted research. By integrating various omics approaches, a comprehensive understanding of molecular interactions and their effects on plant systems can be achieved. This review underscores potential targets for biotechnological and agronomic interventions aimed at enhancing plant resilience by identifying key stress-responsive genes, proteins, and metabolites. Ultimately, this work addresses critical knowledge gaps and highlights the importance of multi-omics strategies in developing sustainable solutions to mitigate the adverse effects of MP/NP pollution in agriculture, thereby ensuring the integrity of food systems and ecosystems.]]> Wed, 31 Dec 1969 19:00:00 EST METTL3-mediated m6A modification in sepsis: current evidence and future perspectives. Wu Z, Miao C, Zhang H
Epigenomics (Apr 2025)

Sepsis, a severe systemic inflammatory condition triggered by infection, is associated with high morbidity and mortality worldwide. While medical diagnosis and treatment have advanced in recent years, a specific therapy remains unavailable. Recently, significant progress has been made in studying the epigenetic RNA modification N6-methyladenosine (m6A) and its core methyltransferase METTL3. The role of m6A in sepsis has also been increasingly elucidated. This review aims to explore the pathological mechanisms of sepsis and its relationship with m6A, focusing on the role of the key m6A writer, METTL3, in sepsis.]]> Wed, 31 Dec 1969 19:00:00 EST The demographic history of populations and genomic imprinting have shaped the transposon patterns in Arabidopsis lyrata. Padilla-García N, Le Veve A, Čermák V, Ä°ltaş Ã–, Contreras-Garrido A, Legrand S, Aury JM, Horvath R, Lafon Placette C
Mol Biol Evol (Apr 2025)

Purifying selection is expected to prevent the accumulation of transposable elements within their host, especially when located in and around genes and if affected by epigenetic silencing. However, positive selection may favour the spread of TEs causing genomic imprinting under parental conflict, as genomic imprinting allows parent-specific influence over resource accumulation to the progeny. Concomitantly, the number and frequency of TE insertions in natural populations are conditioned by demographic events. In this study, we aimed to test how demography and selective forces interact to affect the accumulation of TEs around genes, depending on their epigenetic silencing and with a particular focus on imprinted genes. To this aim, we compared the frequency and distribution of TEs in A. lyrata from Europe and North America. Generally, we found that TE insertions showed a lower frequency when they were inserted in or near genes, especially TEs targeted by epigenetic silencing, suggesting purifying selection at work. We also found that many TEs were lost or got fixed in North American populations during the colonization and the postglacial range expansion from refugia of the species in North America, as well as during the transition to selfing, suggesting a potential "TE load'. Finally, we found that silenced TEs increased in frequency and even tended to reach fixation when they were linked to imprinted genes. We conclude that in A. lyrata, genomic imprinting has spread in natural populations through demographic events and positive selection acting on silenced TEs, potentially under a parental conflict scenario.]]> Wed, 31 Dec 1969 19:00:00 EST Conservation of imprinted expression across genotypes is correlated with consistency of imprinting across endosperm development in maize. Higgins K, Nyabashi V, Anderson S
G3 (Bethesda) (Apr 2025)

Imprinted expression is an essential process for seed viability affecting hundreds of genes in Zea mays endosperm; however, most studies have examined just one time point for analysis. The focus on single time points can limit our ability to identify imprinted genes and our ability to draw conclusions for the role of imprinting in endosperm. In this study, we examine imprinted expression across 4 time points ranging from the transition to endoreduplication from mitotic division through the beginning of programmed cell death. Additionally, we assessed imprinting variation across 8 diverse maize lines, 6 of which have never before been assessed for imprinting. Through this analysis, we identify over 700 imprinted genes with varying consistency across time points including 255 genes imprinted at every time point and 105 genes displaying transient imprinting. We find a correlation between high consistency of imprinting across time and high conservation of parental bias across 8 diverse maize lines reciprocally crossed with B73. Additionally, we identify evidence of imprinting for 3 zein genes that are critical for nutrient accumulation in the endosperm, suggesting that imprinting may play a more important role in seed composition than previously thought. Taken together, this study provides a more holistic view of imprinting variation across time and across genotypes in maize and enables us to more thoroughly investigate the complex imprinting landscape.]]> Wed, 31 Dec 1969 19:00:00 EST