geneimprint : Hot off the Press

'; ?> 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 Wed, 14 May 2025 02:52:53 EDT Wed, 14 May 2025 02:52:53 EDT jirtle@radonc.duke.edu james001@jirtle.com 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 Î²-globin Î¼LCR with a compact enhancer in a Î²-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 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 â¼5 months) and 3-month-old Huntington's disease model mice (lifespan â¼4 months). The detection of BMs in purified CD4+Â 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 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 tefkovÃ¡ 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 Distinct pathways for genetic and epigenetic predisposition in familial and bilateral Wilms tumor. Wegert J, Appenzeller S, Treger TD, Streitenberger H, Ziegler B, Bausenwein S, Vokuhl C, Parks C, JÃ¼ttner E, Gramlich S, Ernestus K, Warman SW, Fuchs J, Hubertus J, von Schweinitz D, FrÃ¶hlich B, Jorch N, KnÃ¶fler R, Friedrich C, Corbacioglu S, FrÃ¼hwald MC, Pekrun A, Schneider DT, Faber J, Stursberg J, Metzler M, Welter N, Pritchard-Jones K, Graf N, FurtwÃ¤ngler R, Behjati S, Gessler M
Genome Med (May 2025)

Genetic predisposition is particularly common in children with the kidney cancer, Wilms tumor. In 10% of these children, this manifests as a family history of Wilms tumor or bilateral disease. The frequency and spectrum of underlying changes have not been systematically investigated.]]> 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 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 (ERÎ±) for proliferation, but little is known about its transcriptional regulation in these tumors.]]> 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 Comprehensive Clinicopathological and Multiomics Characterization of Dermatofibrosarcoma Protuberans Revealed PDGFD Fusion as Distinct Molecular Subtype with Better Survival. Yeung MCF, Fong T, Liu APY, Chan RCK, Chan AZ, Lau WH, Lok J, Gao GY, Leung SY, Shek TWH
Mod Pathol (May 2025)

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive superficial mesenchymal neoplasm characterized by COL1A1::PDGFB fusion. Recently, PDGFD has been identified as a less common fusion partner. However, the clinicopathological and molecular differences between PDGFD and PDGFB fusion DFSP remain largely unknown. In this study of 363 DFSPs, we found 10 cases with PDGFD fusion, including two with a previously undescribed partner involving the EMILIN1 gene. Multi-omics analysis showed distinct transcriptomics, epigenomics, and copy number features for PDGFD fusion DFSP versus PDGFB fusion DFSP. PDGFD fusion DFSP had higher PDGFD expression and virtually no PDGFB expression. Both clustered into the DFSP epigenomic cluster but formed a distinct sub-cluster with differential methylation affecting fibroblast migration genes. Copy number analysis revealed that PDGFD fusion DFSP formed a distinct subgroup with a generally copy number neutral profile and better survival compared to PDGFB fusion DFSP that was dominated by amplification at translocation sites in chromosomes 17 and 22. Pooled analysis of 39 cases (incorporating 29 from the literature) revealed that PDGFD fusion DFSP was more common in females (71.8% vs. 42.4%, p <0.001), occurred at a lower age (Median 37 vs. 45, p < 0.01), and had a higher chance of occurrence at the breast (25.6% vs. 2.3%; p < 0.001). PDGFD fusion DFSP also tended to centre predominantly in the subcutis (63.6% vs. 30%; p < 0.001), had a circumscribed border (50% vs. 19.2%, p < 0.001), was smaller in size (3 cm vs. 3.5 cm, p = 0.017), and had a lower mitotic count (Median 1 vs. 3 per 10 h.p.f., p = 0.03). Overall, our study provided detailed multi-omics characterization of PDGFD fusion DFSP with significant clinico-pathological and diagnostic implications.]]> 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 (54âCD; 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 4âyears of colonoscopy, while a patient's succinotype is associated with a higher frequency of relapses.]]> 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 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 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, BÃ¶rner 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 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 Cell Type-Level Epigenetics at the Frontier of Atherosclerosis Research. Zannas AS
Circulation (May 2025)

]]> 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 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-KÃ¼cÃ¼kgÃ¶ze I, Marques YFS, Joppich M, Kumkum M, RÃ¶Ã 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 Epigenome profiling reveals distinctive regulatory features and cis-regulatory elements in pepper. Yang H, Yu G, Lv Z, Li T, Wang X, Fu Y, Zhu Z, Guo G, He H, Wang M, Qin G, Liu F, Zhong Z, Xue Y
Genome Biol (May 2025)

Pepper (Capsicum annuum) is one of the earliest and most widely cultivated vegetable crops worldwide. While the large and complex genome of pepper severely hampered the understanding of its functional genome, it also indicates a rich yet unexplored reservoir of regulatory elements (REs). In fact, variations in the REs represent a major driving force in evolution and domestication in both plants and animals. However, identification of the REs remains difficult especially for plants with complex genomes.]]> 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 Increasing temporal sensitivity of omics association studies with epigenome-wide distributed lag models. Parikh MN, Manning ER, Niu L, Ruehlmann AK, Folger AT, Brunst KJ, Brokamp C
Am J Epidemiol (May 2025)

Current methods for identifying temporal windows of effect for time-varying exposures in omics settings can control false discovery rates at the biomarker level but cannot efficiently screen for timing-specific effects in high dimensions. Current approaches leverage separate models for site screening and identification of susceptible time windows, and these can miss associations that vary over time. We introduce the epigenome-wide distributed lag model (EWDLM), a novel approach that combines traditional false discovery rate methods with the distributed lag model (DLM) to screen for timing-specific effects in high dimensional settings. This is accomplished by marginalizing DLM effect estimates over time and correcting for multiple comparisons. In a simulation investigating timing-specific effects of ambient air pollution during pregnancy on DNA methylation across the epigenome at age 12Â years, the EWDLM achieved an increased sensitivity for associations limited to specific periods of time compared with traditional 2-stage approaches. In a real-world EWDLM analysis, 353 cytosine-phosphate-guanine sites were identified at which DNA methylation measured at age 12 years was significantly associated with fine particulate matter exposure during pregnancy. The EWDLM provides an efficient and sensitive way to screen epigenomic data sets for associations with exposures localized to specific time periods.]]> Wed, 31 Dec 1969 19:00:00 EST