'; ?> 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, 16 May 2025 02:59:50 EDT Fri, 16 May 2025 02:59:50 EDT jirtle@radonc.duke.edu james001@jirtle.com Emergence of CpG-cluster blanket methylation in aged tissues: a novel signature of epigenomic aging. Kang YK, Min B, Eom J, Park JS, Jang J, Jeong S
Nucleic Acids Res (May 2025)

Aging is accompanied by widespread DNA methylation changes across the genome. While age-related methylation studies typically focus on individual CpGs, cluster analysis provides more robust data and improved interpretation. We characterized age-associated CpG-cluster methylation changes in mouse spleens, peripheral blood mononuclear cells, and livers. We identified a novel signature termed blanket methylations (BMs), fully methylated CpG clusters absent in young tissues but appearing in aged tissues. BM formation was locus- and cell-dependent, with minimal overlap among tissues. Statistical analysis, heterogeneity assessment, and random modeling demonstrated that BMs arise through nonrandom mechanisms and correlate with accelerated aging. Notably, BMs appeared in chronologically young mice with progeroid or disease-driven aging, including in 4-month-old Zmpste24-/- (lifespan ∼5 months) and 3-month-old Huntington's disease model mice (lifespan ∼4 months). The detection of BMs in purified CD4+ T cells demonstrated that their occurrence is intrinsic to aging cells rather than a result of infiltration from other tissues. Further investigation revealed age-related downregulation of zinc-finger-CxxC-domain genes, including Tet1 and Tet3, which protect CpG islands from methylation. Importantly, TET1 or TET3 depletion induced BM formation, linking their loss to age-associated methylation drift. These findings establish BMs as a robust marker of epigenomic aging, providing insight into age-related methylation changes.]]> Wed, 31 Dec 1969 19:00:00 EST Cell Type-Level Epigenetics at the Frontier of Atherosclerosis Research. Zannas AS
Circulation (May 2025)

]]> Wed, 31 Dec 1969 19:00:00 EST Broadening the Nicotiana benthamiana research toolbox through the generation of dicer-like mutants using CRISPR/Cas9 approaches. Bardani E, Katsarou K, Mitta E, Andronis C, Å tefková M, Wassenegger M, Kalantidis K
Plant Sci (Jul 2025)

RNA silencing in plants plays a pivotal role in various biological processes, including development, epigenetic modifications and stress response. Key components of this network are Dicer-like (DCL) proteins. Nicotiana benthamiana encodes four DCLs, each responsible for the generation of distinct small RNA (sRNA) populations, which regulate different functions. However, elucidating the precise role of each DCL has been proven challenging, as overlapping functions exist within DCLs. In our present study, we have successfully generated dcl2, dcl3 and dcl4 homozygous mutants, employing two different CRISPR/Cas9 approaches. The first approach is based on a transgene-mediated delivery of the single-guide RNA (sgRNA), while the second approach employs a viral vector for sgRNA delivery. By utilizing a suite of screening techniques, including polymerase chain reaction (PCR), T7 endonuclease I (T7E1) assay, high-resolution melt analysis (HRMA) and DNA sequencing, we successfully generated dcl2, dcl3 and dcl4 homozygous mutants harboring identical mutations in every allele. To evaluate these dcl mutants, we examined their sRNA profiles and phenotypes. We further have indications that homozygous mutations of a gene do not always lead to the desired loss-of-function, highlighting the importance of mutant evaluation. dcl mutants represent invaluable tools to explore how overlapping silencing pathways are connected to essential plant functions, including development, stress responses and pathogen defense. Additionally, they hold potential for biotechnological applications, such as crop improvement and gene silencing tools. We anticipate that our study will make significant contributions to enhance understanding of the role of DCLs in plants.]]> Wed, 31 Dec 1969 19:00:00 EST Large-scale discovery of potent, compact and erythroid specific enhancers for gene therapy vectors. Psatha N, Sova P, Georgolopoulos G, Paschoudi K, Iwata M, Bloom J, Ulyanova T, Wang H, Kirtsou A, Vasiloudis NI, Wilken MS, Stamatoyannopoulos JA, Yannaki E, Papayanopoulou T, Stamatoyannopoulos G, Vierstra J
Nat Commun (May 2025)

Gene expression during cell development and differentiation is orchestrated by distal regulatory elements that precisely modulate cell selective gene activity. Gene therapy vectors leverage these elements for precise spatiotemporal transgene expression. Here, we develop a one-shot approach to screen candidate regulatory sequences from large-scale epigenomics data for programmable transgene expression within gene therapy viral vectors. We assess a library of 15,000 short sequences derived from developmentally active elements during erythropoiesis using a clinically relevant reporter vector. These elements display a gradient of transcriptional enhancer activity in erythroid cells, with high cell type restriction and developmental stage specificity. Finally, replacing the canonical β-globin μLCR with a compact enhancer in a β-thalassemia lentiviral vector successfully corrects the thalassemic phenotype in patient-derived hematopoietic and stem and progenitor cells (HSPCs), while increasing viral titers and cell transducibility. Our approach provides further insights into enhancer biology with wider implications for human gene therapy.]]> Wed, 31 Dec 1969 19:00:00 EST Development and validation of a machine learning prognostic model based on an epigenomic signature in patients with pancreatic ductal adenocarcinoma. Zaccaria GM, Altini N, Mongelli V, Marino F, Bevilacqua V
Int J Med Inform (Jul 2025)

In Pancreatic Ductal Adenocarcinoma (PDAC), current prognostic scores are unable to fully capture the biological heterogeneity of the disease. While some approaches investigating the role of multi-omics in PDAC are emerging, the analysis of methylation data is under exploited.]]> Wed, 31 Dec 1969 19:00:00 EST Ezh2 Shapes T Cell Plasticity to Drive Atherosclerosis. Bonfiglio CA, Lacy M, Triantafyllidou V, Farina FM, Janjic A, Nitz K, Wu Y, Bazioti V, Avcilar-Kücükgöze I, Marques YFS, Joppich M, Kumkum M, Röß K, Venkatasubramani AV, Imhof A, Enard W, Maegdefessel L, de Winther M, Weber C, Santovito D, Lutgens E, Atzler D
Circulation (May 2025)

The activation and polarization of T cells play a crucial role in atherosclerosis and dictate athero-inflammation. The epigenetic enzyme EZH2 (enhancer of zeste homolog 2) mediates the H3K27me3 (trimethylation of histone H3 lysine 27) and is pivotal in controlling T cell responses.]]> Wed, 31 Dec 1969 19:00:00 EST Precision Health: Applications for Registered Nurses. Davis SH, Himes DO, Dewell S, Dungan JR, Lucas RF
Nurs Clin North Am (Jun 2025)

Precision health care requires the treatment of individuals, families, communities, and populations based on their genomic, biological, behavioral, and environmental characteristics. Nurses are key factors in identifying health risk factors and coordinating treatment plans." to "Nurses are essential healthcare professionals who identify health risk factors and coordinate treatment plans. Genomics-informed nurses can improve patient outcomes by advocating for appropriate care plans or riskprevention strategies at the individual, family, community, and population levels. Social determinants of health and the resulting epigenomic modifications are important factors to integrate into care plans. Genomics-informed nursing care incorporates genetic and genomic knowledge in the nursing process to promote optimal outcomes through precision health care.]]> Wed, 31 Dec 1969 19:00:00 EST Endometrial tumorigenesis involves epigenetic plasticity demarcating non-coding somatic mutations and 3D-genome alterations. Gregoricchio S, Kojic A, Hoogstraat M, Schuurman K, Stelloo S, Severson TM, O'Mara TA, Droog M, Singh AA, Glubb DM, Wessels LFA, Vermeulen M, van Leeuwen FE, Zwart W
Genome Biol (May 2025)

The incidence and mortality of endometrial cancer (EC) is on the rise. Eighty-five percent of ECs depend on estrogen receptor alpha (ERα) for proliferation, but little is known about its transcriptional regulation in these tumors.]]> Wed, 31 Dec 1969 19:00:00 EST Premalignant lesions of the oral cavity: a narrative review of factors and mechanisms of transformation into cancer. Prostakishina EA, Sidenko EA, Kolegova ES, Patysheva MR, Kononova GA, Choinzonov EL
Int J Oral Maxillofac Surg (Jun 2025)

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer. The development and progression of OSCC are closely linked to various aetiological factors. Early signs of OSCC may manifest as oral lesions, genetic abnormalities, and chronic inflammation. Lesions with dysplastic features have a high risk of malignant transformation into OSCC. Moreover, dysplastic lesions are characteristic of many oral potentially malignant disorders (OPMDs). Currently, there is no unified standard of treatment for OPMD patients, due to the variability in risk factors and mechanisms of transformation. Therefore, it is essential to detect and manage OPMDs at an early stage in order to prevent their malignant transformation into OSCC. This necessitates analysing OPMD mechanisms to identify objective markers for predicting the risk of malignant transformation. The aim of this review was to describe the process of OPMD transformation into OSCC under the influence of environmental, immune, microbiome, and molecular factors.]]> 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 NSD1 mutation status determines metabolic inhibitor sensitivity in head and neck squamous cell carcinomas by regulating mitochondrial respiration. Tang S, Wang Q, Wang Z, Cai L, Pan D, Li J, Chen Q, Zhou Y, Shen YQ
J Pathol (May 2025)

Head and neck squamous cell carcinomas (HNSCCs) are the most common malignant tumors in the head and neck region, characterized by a high recurrence rate and early metastasis. Despite advances in treatment, patient outcomes and prognosis remain poor, highlighting the urgent need for new therapeutic strategies. Recent research has increasingly focused on targeting glucose metabolism as a therapeutic strategy for cancer, revealing multiple promising targets and potential drugs. However, the metabolic heterogeneity among tumors leads to variable sensitivity to metabolic inhibitors in different patients, limiting their clinical utility. In this study, we employed bioinformatics analysis, cell experiments, animal models, and multi-omics approaches to reveal differences in glucose metabolism phenotypes among HNSCC patients and elucidated the underlying molecular mechanisms driving these differences. Our findings showed that NSD1 mutation status affects the glucose metabolism phenotype in HNSCC, with NSD1 wild-type HNSCC exhibiting higher mitochondrial respiration and NSD1 mutant HNSCC showing weaker mitochondrial respiration but enhanced glycolysis. We further demonstrated that NSD1 regulates mitochondrial respiration in HNSCC via epigenetic modulation of the TGFB2/PPARGC1A signaling axis. Additionally, we found that NSD1 wild-type HNSCC is more sensitive to mitochondrial respiration inhibitors, whereas NSD1 mutant HNSCC shows increased sensitivity to glycolysis inhibitors. In summary, we found that NSD1 can epigenetically regulate the TGFB2/PPARGC1A axis to modulate mitochondrial respiration and sensitivity to metabolic inhibitors in HNSCC. These findings suggest a novel strategy for selecting metabolic inhibitors for HNSCC based on the NSD1 gene status of patients. © 2025 The Pathological Society of Great Britain and Ireland.]]> Wed, 31 Dec 1969 19:00:00 EST Safeguarding genomic imprints in naive human pluripotency. De Los Angeles A
Stem Cell Reports (May 2025)

Naive human pluripotent stem cells (hPSCs) closely mirror the pre-implantation epiblast but risk imprint erosion under strong MEK/ERK inhibition, jeopardizing disease modeling and regenerative applications. In Stem Cell Reports, Fischer et al. show that partial MEK/ERK inhibition plus ZFP57 overexpression crucially preserves parent-of-origin DNA methylation, thereby offering more faithful and stable naive hPSC models.]]> Wed, 31 Dec 1969 19:00:00 EST Pathogenomic fingerprinting to identify associations between tumor morphology and epigenetic states. Monabbati S, Corredor G, Pathak T, Peacock C, Yang K, Koyfman S, Scacheri P, Lewis J, Madabhushi A, Viswanath SE, Gryder B
Eur J Cancer (May 2025)

Measuring the chromatin state of a tumor provides a powerful map of its epigenetic commitments; however, as these are generally bulk measurements, it has not yet been possible to connect changes in chromatin accessibility to the pathological signatures of complex tumors. In parallel, recent advances in computational pathology have enabled the identification of spatial features and immune cells within oral cavity tumors and their microenvironment.]]> Wed, 31 Dec 1969 19:00:00 EST From Multi-Omics to Visualization and Beyond: Bridging Micro and Macro Insights in CAR-T Cell Therapy. Gong Y, Fei P, Zhang Y, Xu Y, Wei J
Adv Sci (Weinh) (May 2025)

Chimeric antigen receptor T (CAR-T) cell therapies, a cornerstone of immunotherapy, have demonstrated remarkable efficacy in treating hematological malignancies and have more recently expanded into applications for solid tumors and autoimmune diseases. Emerging multidimensional profiling technologies offer promising solutions for enhancing CAR-T efficacy, overcoming resistance, and facilitating the development of novel CAR-T constructs. The integration of genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics enables a comprehensive understanding of the intrinsic mechanisms underlying CAR-T therapy, while single-cell and spatial omics significantly improve data resolution and analytical depth. Coupled with advances in biomedical engineering, visualization technologies form the foundation for omics data generation by bridging microscopic and macroscopic scales and enabling dynamic, 3D in vivo monitoring of CAR-T behavior. Artificial intelligence (AI) further supports this framework by enabling the analysis of complex, high-dimensional datasets. This review highlights recent advances in the integration of multidimensional omics within CAR-T therapy and explores cutting-edge developments in visualization technologies and AI applications. The full convergence of multi-omics, visualization tools, and AI is poised to deliver transformative insights into the mechanisms governing CAR-T cell therapy.]]> Wed, 31 Dec 1969 19:00:00 EST Associations of epigenetic aging with self-rated health, access to care, and healthcare utilization in a representative sample of United States adults. Nwanaji-Enwerem JC, Khodasevich D, Gladish N, Shen H, Bozack AK, Daredia S, Needham BL, Rehkopf DH, Cardenas A
Clin Epigenetics (May 2025)

Health status is closely linked to both healthcare access and utilization. While previous research has identified associations between health status and DNA methylation-based biomarkers of aging (epigenetic aging), studies exploring these relationships in the context of healthcare access and utilization remain limited. To address this gap, we analyzed cross-sectional associations in a representative sample of 2,343 U.S. adults from the 1999-2000 and 2001-2002 cycles of the National Health and Nutrition Examination Survey (NHANES). Our study examined the relationships of self-rated health status, healthcare access, and healthcare utilization with seven epigenetic aging biomarkers: HannumAge, HorvathAge, SkinBloodAge, PhenoAge, GrimAge2, DNAm Telomere Length (DNAmTL), and DunedinPoAm.]]> Wed, 31 Dec 1969 19:00:00 EST The predictive power of profiling the DNA methylome in human health and disease. Christofidou P, Bell CG
Epigenomics (May 2025)

Early and accurate diagnosis significantly improves the chances of disease survival. DNA methylation (5mC), the major DNA modification in the human genome, is now recognized as a biomarker of immense clinical potential. This is due to its ability to delineate precisely cell-type, quantitate both internal and external exposures, as well as tracking chronological and biological components of the aging process. Here, we survey the current state of DNA methylation as a biomarker and predictor of traits and disease. This includes Epigenome-wide association study (EWAS) findings that inform Methylation Risk Scores (MRS), EpiScore long-term estimators of plasma protein levels, and machine learning (ML) derived DNA methylation clocks. These all highlight the significant benefits of accessible peripheral blood DNA methylation as a surrogate measure. However, detailed DNA methylation biopsy analysis in real-time is also empowering pathological diagnosis. Furthermore, moving forward, in this multi-omic and biobank scale era, novel insights will be enabled by the amplified power of increasing sample sizes and data integration.]]> Wed, 31 Dec 1969 19:00:00 EST Tissular chromatin states cartography based on double-barcoded DNA arrays capturing unloaded PA-Tn5 Transposase. Mendoza-Ferri MG, Lozachmeur G, Duvina M, Perret L, Merciris D, Gigout A, Mendoza-Parra MA
Genome Res (May 2025)

Recent developments in spatial omics are revoluzionating our understanding of tissue structures organization and their deregulation in disease. Here, we present a strategy for capturing chromatin histone modification signatures across tissue sections by taking advantage of a double-barcoded DNA arrays design compatible with in situ protein A-Transposase Tn5 tagmentation. This approach has been validated in presence of fresh-frozen mouse brain tissues but also in decalcified formalin-fixed paraffin-embedded (FFPE) mouse paws samples, where either the histone modification H3K4 tri-methylation or H3K27-acethylation has been used as proxy for interrogating active promoter signatures. Furthermore, since combinatorial enrichment of multiple histone modifications were shown to code for various states of gene transcriptional status (active, bivalent, repressed), we have integrated several histone modifications issued from consecutive mouse embryos to reveal changes in chromatin states across the tissue. Overall, this spatial epigenomics technology combined with the use of a spatial chromatin states analytical strategy paves the way for future epigenetics studies for addressing tissue architecture complexity.]]> Wed, 31 Dec 1969 19:00:00 EST ChromActivity: integrative epigenomic and functional characterization assay based annotation of regulatory activity across diverse human cell types. Dincer TU, Ernst J
Genome Biol (May 2025)

We introduce ChromActivity, a computational framework for predicting and annotating regulatory activity across the genome through integration of multiple epigenomic maps and various functional characterization datasets. ChromActivity generates genomewide predictions of regulatory activity associated with each functional characterization dataset across many cell types based on available epigenomic data. It then for each cell type produces ChromScoreHMM genome annotations based on the combinatorial and spatial patterns within these predictions and ChromScore tracks of overall predicted regulatory activity. ChromActivity provides a resource for analyzing and interpreting the human regulatory genome across diverse cell types.]]> Wed, 31 Dec 1969 19:00:00 EST Mapping stress memory: genetic and epigenetic insights into combined drought and heat tolerance in barley. Elkelish A, Alqudah AM, Alhudhaibi AM, Alqahtani H, Saied EM, Börner A, Thabet SG
Plant Cell Rep (May 2025)

Unveiling genetic and epigenetic mechanisms in barley, this study maps stress memory under combined drought and heat, advancing resilience breeding for climate-adaptive crop improvement. Barley is one of the world's most important cereal crops and is increasingly threatened by concurrent drought and heat stress, two major environmental factors intensified by climate change. In our study, we employed a genome-wide association scan (GWAS) to investigate the concept of "stress memory," wherein barley plants exposed to previous stress events exhibit enhanced responses to subsequent ones. We evaluated key agronomic traits, such as plant height, spike length, grain number, and thousand kernel weight along with biochemical markers such as chlorophyll content, proline, and soluble proteins across three generations under combined drought and heat stress. This approach encompassed transgenerational and intergenerational stress memory and a third generation that could reveal the potential cumulative effects of combined drought and heat stress. Our findings demonstrated a significant increase in metabolites specifically proline and soluble proteins in third-generation barley plants compared to those exposed to stress for only one or two generations. Through GWAS analysis, we identified 332 highly significant SNP markers clustered within 14 genomic regions on chromosomes 2H, 3H, 4H, 5H, and 7H. These regions are associated with all evaluated physiological and morphological traits under stress that harbor several potential candidate genes implicated in regulating complex signaling pathways, reactive oxygen species scavenging, and energy metabolism processes essential for mitigating the impacts of drought and heat. These results underscore the intricate nature of barley's stress tolerance mechanisms and highlight the potential for integrating genomics, epigenomics, and advanced phenotyping approaches into breeding programs.]]> Wed, 31 Dec 1969 19:00:00 EST Chromatin Rewiring by SETD2 Drives Lipotoxic Injury in Cardiometabolic HFpEF. Costantino S, Mohammed SA, Ambrosini S, Telesca M, Mengozzi A, Walavalkar K, Gorica E, Herwig M, van Heerebeek L, Xia J, Karsai G, Hornemann T, Dzemali O, Santoro R, Lin Q, Ruschitzka F, Hamdani N, Paneni F
Circ Res (May 2025)

Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is a highly prevalent and deadly condition. Histone 3 trimethylation at lysine 36 (H3k36me3)-a chromatin signature induced by the histone methyltransferase SETD2 (SET domain containing 2)-correlates with changes in gene expression in human failing hearts; however, its role remains poorly understood. This study investigates the role of SETD2 in cHFpEF.]]> Wed, 31 Dec 1969 19:00:00 EST