'; ?> 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 Thu, 08 Jan 2026 01:42:25 EST Thu, 08 Jan 2026 01:42:25 EST jirtle@radonc.duke.edu james001@jirtle.com Genetic and epigenetic insights into systemic lupus erythematosus: linking long non-coding RNA growth arrest-specific transcript 5 and interferon signature. Maghraby GG, El-Menyawi MA, Rehiem HAA, Shaker OG, Habib MM, Elgohary R
J Rheum Dis (Jan 2026)

Interferon (IFN) signaling, and excessive apoptosis have a well-established role in systemic lupus erythematosus (SLE) pathogenesis. Long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been linked to excessive apoptosis and upregulation of IFN genes. We aimed to investigate the expression of IFN-stimulated genes in SLE patients compared to healthy controls, and to assess their association with lncRNA GAS5 and clinical characteristics of SLE.]]> Wed, 31 Dec 1969 19:00:00 EST The superpowers of imprinting control regions. Montibus B, Court F, Arnaud P
Genome Res (Jan 2026)

Genomic imprinting is a specialized mechanism of transcriptional regulation whereby approximately 200 mammalian genes are expressed monoallelically according to their parental origin. This crucial developmental process is primarily controlled by discrete -regulatory elements known as imprinting control regions (ICRs), which play essential roles in directing allele-specific gene expression across large imprinted domains. In this review, we highlight the features that define ICRs as a distinct class of -regulatory regions, from their ability to maintain germline-inherited DNA methylation to their multifunctional roles in transcriptional control. For each imprinted domain, we examine the diverse mechanisms by which individual ICRs integrate multiple regulatory functions to coordinate both proximal and distal imprinted gene expression. By uncovering the multifaceted roles of ICRs, this review provides a compelling framework for understanding, more broadly, the molecular basis of finely controlled gene expression.]]> Wed, 31 Dec 1969 19:00:00 EST CRISPR 2.0: Expanding the genome engineering Toolbox for epigenetics, RNA editing, and molecular diagnostics. Pradhan K, Anoop S
Gene (Feb 2026)

Non-canonical CRISPR systems adaptation has led to genome editing through nucleases, and the development of transcriptional and epigenetic regulation, transcriptome editing, and molecular diagnostics has resulted in a diversified set of tools-CRISPR 2.0. In this review, the author summarizes the mechanisms and recent engineering advances of (i) dCas9-based epigenetic effectors, (ii) RNA-targeting Cas13 systems and engineered RNA editors, (iii) DNA base editors and prime editors, and (iv) CRISPR-powered diagnostic platforms and their translational readiness. There is a critical comparison of the various approaches (e.g., RNAi/ASO versus Cas13-based methods; base editing versus prime editing) along with practical translational considerations such as delivery technologies, safety (off-target/edit windows, mosaicism), and regulatory pathways which are evaluated. Three concise case studies refer to map laboratory evidence to clinical or near-clinical outcomes and the ethical and governance discussion is widened to include global access, intellectual property and equity in deployment. Finally, the authors classify technologies according to their level of readiness - diagnostics and some ex-vivo therapeutic approaches are already in or very close to clinical use, chosen in-vivo editing methods are undergoing early trials, and AI-assisted nuclease design is still mostly theoretical but is getting better fast. This comprehensive viewpoint is intended to help researchers and physicians understand which CRISPR tools are most likely to be translated soon and where more validation is required.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomic alterations and neural development anomalies in induced pluripotent stem cells from sporadic Alzheimer's disease. Katbe A, Hanna R, Flamier A, Serhani D, Hamam R, Barabino A, Tavares E, Héon Ã‰, Bernier G
Development (Jan 2026)

Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) resets the aging clock. However, primed iPSCs can retain cell-of-origin epigenomic marks, especially those linked to heterochromatin. Here, we show that iPSCs produced from fibroblasts of late-onset sporadic Alzheimer's disease (AD) cases retain epigenomic alterations that correlate with developmental anomalies and neurodegeneration. Compared to controls, AD iPSCs show reduced BMI1 expression and H3K9me3 levels and an altered DNA methylome. Gene Ontology analysis of differentially methylated DNA regions reveals terms linked to cell-cell adhesion and synapses, with MEF2C-binding sites being the most enriched at differentially methylated DNA regions. Upon noggin exposure, AD iPSCs show less-efficient neural induction and forebrain specification, together with elevated WNT signaling. Mature AD neurons present a mixed cell lineage identity phenotype and reduced MEF2C expression. AD glial cells express neuronal, cell proliferation, and stem cell-related genes. Despite these anomalies, AD iPSCs generate cortical neurons in normal proportion and readily form cerebral organoids showing AD-related pathologies. These findings implicate reprogramming-resistant epigenomic alterations or genetic variants working in trans on the epigenome in AD pathophysiology.]]> Wed, 31 Dec 1969 19:00:00 EST A smoothing method for DNA methylome analysis to enhance epigenomic signature detection in epigenome-wide association studies. Oussalah A, Mousel L, Trégouët DA, Guéant JL
Methods (Feb 2026)

Epigenome-wide association studies (EWAS) are instrumental for mapping DNA methylation changes in human traits and diseases but often suffer from low statistical power and false positives, especially in small cohorts. We developed an EWAS smoothing method that exploits co-methylation of adjacent CpG probes within CpG islands via a sliding-window average and generalized it using Savitzky-Golay filtering. We applied the smoothing approach-with window widths of 1-3 CpGs and, for generalization, Savitzky-Golay filters of varying polynomial orders and window sizes-across five distinct EWAS settings. Performance was quantified by signal-to-noise ratio (SNR), noise-variance reduction, variance ratio (VR), Bayes factors, and sample-size sensitivity. In the MMACHC epimutation dataset, a 5-CpG window (width, w = 2) increased SNR by 90 %, reduced noise variance by 80 %, and elevated VR by 176 % at the target CpG island, with no genome-wide false positives. For MLH1, smoothing preserved the top association and suppressed background signals. In the aging EWAS, a "Polyepigenetic CpG aging score" was derived following smoothing. This score correlated strongly with chronological age in the discovery cohort (Spearman's ρ = 0.89; P = 3.0 × 10) and was independently validated in a separate dataset, significantly distinguishing newborns from nonagenarians (P = 3.4 × 10). Savitzky-Golay filtering of order 0 with a 5-CpG window yielded optimal SNR across bootstrap iterations, supporting this configuration as a robust choice for methylation array smoothing. As an extension of the Savitzky-Golay-based smoothing framework, reanalysis of a liver cancer dataset identified five top loci surpassing a smoothed P-value threshold of 1 × 10. Among these, MIR10A within the HOXB3 locus was the only previously reported functionally relevant site. In conclusion, the smoothing method improves EWAS performance by enhancing SNR, enabling detection of meaningful associations even in small cohorts, and offers a valuable tool for reanalyzing existing Infinium methylation array datasets to uncover previously undetected epigenomic signatures.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic Modulation of Immunity: Mechanisms, Implications, and Emerging Therapeutic Horizons; a Step Toward Epigenetics to Precision. Saleh DO, Salem ML, Van Linthout S, Lin Q, Hamdy NM
Subcell Biochem (2026)

Epigenetic regulation plays a central role in immune cell development, specialization, and memory formation by dynamically modifying DNA, histones, and RNA. These processes enable adaptation to environmental cues, precise pathogen responses, and maintenance of immune tolerance, while their disruption contributes to autoimmune, inflammatory, and cancer pathogenesis. DNA methylation, histone modifications, and noncoding RNA regulation shape the lineage and activation states of T cells, B cells, macrophages, and natural killer (NK) cells, with specific alterations linked to diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Emerging insights also highlight roles for RNA modifications and exosome-mediated RNA transfer in immune activation, trained immunity, and antigen presentation. Advances in single-cell epigenomics, CRISPR-based editing, and RNA sequencing are driving the development of targeted therapies-such as DNA methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, RNA-based interventions, and exosome delivery systems-that aim to reprogram immune responses. Understanding immune cell epigenetics paves the way for precision immunotherapies tailored to patient-specific profiles, offering highly specific, effective treatments with minimal immune suppression.]]> Wed, 31 Dec 1969 19:00:00 EST TALE Homeodomain Proteins in Plant Reproductive Development and Environmental Stress Resilience. Niu X, Jiang X, Li H, Qin R, Qin Y
Plant Cell Environ (Feb 2026)

TALE (Three Amino acid Loop Extension) homeodomain transcription factors are key conserved elements in eukaryotic developmental patterning. In plants, this superclass divides into the KNOX and BELL families, which are essential for regulating meristem maintenance, organogenesis, and tissue identity. Recent advances show that TALE proteins are intricately involved in plant reproductive processes, including gametophyte differentiation, embryonic axis formation, and floral organogenesis. They function as molecular scaffolds, integrating spatiotemporal signals and hormonal signaling like auxin, cytokinin, and gibberellin to control phase transitions and reproductive cell fate determination. The lineage-specific expansions and domain rearrangements of TALE genes across bryophytes, gymnosperms, and angiosperms indicate repeated co-option and neofunctionalization throughout land plant evolution. Emerging insights from epigenomics and protein interactomes reveal that TALE complexes modulate cell type-specific transcriptional responses. This review synthesizes current understanding of TALE-mediated regulatory networks during plant reproductive development and presents a conceptual framework for investigating their roles in developmental plasticity and stress-responsive fertility. We also highlight opportunities to utilize TALE-based regulatory modules to develop climate-resilient crops through multi-omics and genome editing approaches. Decoding the reproductive logic embedded in TALE networks offers transformative potential for reprogramming plant development in an era of agricultural and ecological uncertainty.]]> Wed, 31 Dec 1969 19:00:00 EST Dissecting neuroblastoma heterogeneity through single-cell multi-omics: insights into development, immunity, and therapeutic resistance. He GQ, He SJ, Jing XY, Dai YL, Guo X, Gao J, Zhang W
Oncogene (Jan 2026)

Neuroblastoma (NB), the most common extracranial solid tumor in children, is characterized by remarkable cellular heterogeneity and clinical variability ranging from spontaneous regression to aggressive progression and relapse. Despite advances in multimodal therapies, including surgery, chemotherapy, radiotherapy, differentiation therapy, and immunotherapy-treatment resistance remains the principal barrier to improving survival in high-risk patients. Recent single-cell and spatial multi-omics studies have revolutionized our understanding of NB by revealing its developmental origins, lineage hierarchy, and adaptive evolution under therapeutic pressure. These technologies have delineated distinct cellular states along an adrenergic-mesenchymal continuum and uncovered the dynamic interplay between tumor cells and their microenvironment. Genetic instability, epigenetic reprogramming, and metabolic plasticity cooperate with immune and stromal remodeling to drive tumor persistence and relapse. At the molecular level, mechanisms such as MYCN-driven chromatin remodeling, super-enhancer reorganization, bypass signaling activation, quiescent persister programs, immune checkpoint engagement, and metabolic rewiring collectively enable therapeutic escape. Importantly, these processes are reversible, highlighting tumor plasticity as both a hallmark and a potential vulnerability of NB. Integrating single-cell transcriptomics, epigenomics, and spatial profiling provides an unprecedented framework to map resistance evolution, identify lineage-specific vulnerabilities, and guide rational combination strategies. Targeting epigenetic regulators, metabolic checkpoints, and immune suppressive networks in a temporally coordinated manner holds promise for converting NB from an adaptive to a controllable disease.]]> Wed, 31 Dec 1969 19:00:00 EST Detection of Isodisomy Utilizing SNP Microarray: Frequency, Ascertainment, and Implications. Molinari S, Williams N, Haskell G, Penton A, Arreola A, Gadi I, Phillips K, Tepperberg J, Schwartz S
Am J Med Genet A (Feb 2026)

This study investigates the frequency, ascertainment, and clinical implications of whole chromosomal isodisomy using a database of over 415,000 chromosomal microarray (CMA) tests conducted since 2008 across prenatal, postnatal, and products of conception specimens. In this cohort, 0.04% of cases exhibited the rare chromosomal phenomenon of isodisomy. Analysis of these cases revealed distinct patterns in frequency, chromosome involvement, and parent of origin related to specimen type. Isodisomy 14 was most frequent in prenatal samples, while chromosomes 6, 7, and 15 were more common in postnatal cases. The involvement of imprinted and non-imprinted chromosomes was equivalent for prenatal cases, while imprinted chromosomes consisted of two-thirds of postnatal cases, with paternal uniparental isodisomy more prevalent than maternal across all specimen types. Several cases demonstrated unmasking of pathogenic variants in recessive genes, and findings support prior studies of associations between isodisomy 11 and prenatal or neonatal lethality. These results underscore the diagnostic value of CMA and contribute to an extended understanding of isodisomy's clinical relevance.]]> Wed, 31 Dec 1969 19:00:00 EST A cell type enrichment analysis tool for brain DNA methylation data (CEAM). Müller J, Laroche VT, Imm J, Weymouth L, Harvey J, Reijnders RA, Smith AR, van den Hove D, Lunnon K, Cavill R, Pishva E
Epigenetics (Dec 2026)

DNA methylation (DNAm) signatures are highly cell type-specific, yet most epigenome-wide association studies (EWAS) are performed on bulk tissue, potentially obscuring critical cell type-specific patterns. Existing computational tools for detecting cell type-specific DNAm changes are often limited by the accuracy of cell type deconvolution algorithms. Here, we introduce CEAM (Cell-type Enrichment Analysis for Methylation), a robust and interpretable framework for cell type enrichment analysis in DNA methylation data. CEAM applies over-representation analysis with cell type-specific CpG panels from Illumina EPIC arrays derived from nuclei-sorted cortical post-mortem brains from neurologically healthy aged individuals. The constructed CpG panels were systematically evaluated using both simulated datasets and published EWAS results from Alzheimer's disease, Lewy body disease, and multiple sclerosis. CEAM demonstrated resilience to shifts in cell type composition, a common confounder in EWAS, and remained robust across a wide range of differentially methylated positions, when upstream modeling of cell type composition was modeled with sufficient accuracy. Application to existing EWAS findings generated in neurodegenerative diseases revealed enrichment patterns concordant with established disease biology, confirming CEAM's biological relevance. The workflow is publicly available as an interactive Shiny app (https://um-dementia-systems-biology.shinyapps.io/CEAM/) enabling rapid, interpretable analysis of cell type-specific DNAm changes from bulk EWAS.]]> Wed, 31 Dec 1969 19:00:00 EST Maternal UPD(20) Leading to Mulchandani-Bhoj-Conlin Syndrome: A Rare Neonatal Case With Additional TRPS1 Deletion. Zhang J, Chen X, Chen M, Wu S, Huang F, Pan R, Chen G
Am J Med Genet A (Feb 2026)

Mulchandani-Bhoj-Conlin syndrome is an extremely rare imprinting disorder caused by maternal uniparental disomy of chromosome 20, primarily characterized by intrauterine growth restriction, severe postnatal growth failure, and feeding difficulties. Here, we report a neonate diagnosed with Mulchandani-Bhoj-Conlin syndrome via whole exome sequencing and copy number variation analysis, which also identified a 0.26 Mb deletion on chromosome 8q23.3 affecting the TRPS1 gene, associated with Trichorhinophalangeal syndrome. We describe the clinical features and genetic findings of this infant, with the aim of contributing to a better understanding of these two rare diseases.]]> Wed, 31 Dec 1969 19:00:00 EST Erythropoietin Expression and Regulation: Piecing Together Known Mechanisms and Emerging Insights. Idriss S, Hoogewijs D, Girodon F, Gardie B
Am J Hematol (Jan 2026)

Erythropoietin (EPO) is a circulating glycoprotein hormone essential for red blood cell production. The history of EPO stretches from early observations of hypoxia in the mid-19th century to its gene cloning and the clinical use of recombinant forms. Structurally, EPO's extensive glycosylation shapes stability, receptor binding, and therapeutic potential, inspiring engineered analogs with distinct pharmacokinetics. Developmentally, EPO expression shifts from embryonic neural crest and fetal hepatocytes to renal interstitial fibroblasts after birth. EPO gene regulation integrates hypoxia-inducible factors, transcriptional repressors, enhancers, with HIF-2α as the principal activator, and post-translational mechanisms. Recent findings reveal genetic variants within the EPO gene in patients with erythrocytosis. Isoelectric focusing profiles of EPO in these patients was similar to the hepatic-derived EPO profiles in premature newborns, highlighting a dynamic and context-dependent regulation. These findings suggest that reactivation of EPO expression in the liver could be therapeutically valuable, given that hepatic-derived EPO exhibits enhanced activity. Clinically, erythropoiesis-stimulating agents transformed anemia management but raised safety concerns, leading to refined guidelines. The recent introduction of hypoxia-inducible factor prolyl hydroxylase inhibitors represents a new strategy that restores endogenous EPO production and coordinates iron metabolism through transient HIF stabilization. Outstanding challenges include the absence of faithful human EPO-producing cell models and incomplete understanding of the full molecular mechanisms controlling EPO expression and production. Combining insights from developmental biology, genetics, and epigenomics may open new avenues for therapies targeting disorders of erythropoiesis and oxygen homeostasis.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution. Furlano K, Keshavarzian T, Biernath N, Fendler A, de Santis M, Weischenfeldt J, Lupien M
Int J Cancer (Jan 2026)

Prostate cancer is a common malignancy that in 5%-30% leads to treatment-resistant and highly aggressive disease. Metastasis-potential and treatment-resistance is thought to rely on increased plasticity of the cancer cells-a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases. As cellular plasticity is largely driven by non-genetic events, complementary studies in cancer epigenomics are now being conducted to identify chromatin variants. These variants, defined as genomic loci in cancer cells that show changes in chromatin state due to the loss or gain of epigenomic marks, inclusive of histone post-translational modifications, DNA methylation and histone variants, are considered the fundamental units of epigenomic heterogeneity. In prostate cancer chromatin variants hold the promise of guiding the new era of precision oncology. In this review, we explore the role of epigenomic heterogeneity in prostate cancer, focusing on how chromatin variants contribute to tumor evolution and therapy resistance. We therefore discuss their impact on cellular plasticity and stochastic events, highlighting the value of single-cell sequencing and liquid biopsy epigenomic assays to uncover new therapeutic targets and biomarkers. Ultimately, this review aims to support a new era of precision oncology, utilizing insights from epigenomics to improve prostate cancer patient outcomes.]]> Wed, 31 Dec 1969 19:00:00 EST The Right Person, the Right Treatment, at the Right Time in Alzheimer's Disease: Insights From the 2025 Brain Aging Symposium. de Magalhães CG, Moldakozhayev A, Lopez MV, Bowman GL, Chhatwal JP, Kellis M, Mohs R, Nisenbaum L, Quiroz YT, Raju RM, Sperling RA, Moqri M, Gladyshev VN
Aging Cell (Jan 2026)

On October 22nd, 2025, Brain Aging Symposium took place at Harvard Medical School bringing together leading researchers from academia and partner organizations to discuss recent advances in measuring and monitoring human brain aging trajectories, with a particular focus on Alzheimer's disease (AD). A central theme emerged: achieving "the right treatment for the right person and the right time" through precision medicine approaches. Key advances included the unprecedented validation of plasma-based biomarkers, particularly brain-derived p-Tau217 that can identify seeding AD pathology with remarkable specificity, making large-scale screening newly feasible. Integrating multi-level "omic" modalities, spanning genetic information, molecular biomarkers of nutrition, lipid and protein signatures, neuroimaging measures, cognitive assessments, and lifestyle factors, enhances disease risk modeling and trajectory prediction beyond the capacity of any single marker. Early findings highlight critical roles for nutritional and lipid metabolism, and myelin integrity in brain aging, with cell and sex-specific vulnerabilities identified in response to nutrition, social isolation, and metabolic stress. Computational approaches that combine single-cell genomics, epigenomics, and artificial intelligence have been shown to accelerate causal discovery and therapeutic development. However, significant challenges remain: current biomarkers explain only half the variance in cognitive decline, racial and ethnic differences in biomarker levels lack mechanistic understanding, and scalable tools for comprehensive brain aging assessment are needed. The symposium underscored that preventing AD will require intervening during the preclinical asymptomatic phase. These multimodal screening platforms, coupled with mechanistically driven therapeutics, reduction in modifiable risk factors, including nutrition, vascular health, and social determinants of health, could profoundly impact the field.]]> Wed, 31 Dec 1969 19:00:00 EST A hitchhiker's guide to single-cell epigenomics: Methods and applications for cancer research. Moreno-Gonzalez M, Sierra I, Kind J
Int J Cancer (Jan 2026)

Genetic mutations are well known to influence tumorigenesis, tumor progression, treatment response and relapse, but the role of epigenetic variation in cancer progression is still largely unexplored. The lack of epigenetic understanding in cancer evolution is in part due to the limited availability of methods to examine such a heterogeneous disease. However, in the last decade the development of several single-cell methods to profile diverse chromatin features (chromatin accessibility, histone modifications, DNA methylation, etc.) has propelled the study of cancer epigenomics. In this review, we detail the current landscape of single-omic and multi-omic single-cell methods with a particular focus on the examination of histone modifications. Furthermore, we provide recommendations on both the application of these methods to cancer research and how to perform initial computational analyses. Together, this review serves as a referential framework for incorporating single-cell methods as an important tool for tumor biology.]]> Wed, 31 Dec 1969 19:00:00 EST Machine learning and multi-omics-based identification of hub paternal imprinted genes PEG11/RTL1, PEG9/DLK1, PEG6/NDN, and PEG5/NNAT in sperm of couples experiencing idiopathic recurrent pregnancy loss. Hashemi Karoii D, Najafi SMA, Favaedi R, Esmaeili Borzabadi V, Sabbaghian M, Amirchaghmaghi E, Shahhoseini M
Comput Biol Med (Jan 2026)

Idiopathic recurrent pregnancy loss (IRPL), defined as two or more consecutive pregnancy losses without an identifiable cause, affects 1-2 % of couples in their reproductive years. While maternal factors have been extensively studied, paternal contributions remain underexplored. Paternally imprinted genes are essential for spermatogenesis, embryonic development, and placental function, and their epigenetic dysregulation may contribute to IRPL.]]> Wed, 31 Dec 1969 19:00:00 EST Deciphering Sjögren's disease: New insights and perspectives extend from advanced omics approaches and immunology. Chen H, Kaneko N, Ohyama Y, Moriyama M
J Autoimmun (Jan 2026)

Sjögren's disease (SjD), formerly termed Sjögren's syndrome, is a chronic autoimmune exocrinopathy that has seen substantial advances in basic research over the past decade. Classical experimental approaches have revealed immune dysregulation encompassing aberrant activation of the adaptive immune system, activation of humoral autoimmunity against autoantigens, and upstream participation of innate immune mechanisms. In parallel, with the rapid development of sequencing and omics technologies, researchers are able to use these high-throughput methods to gain a more unbiased, sytem-wide view of disease processes and pathegenesis in SjD. Among them, numerous disease-associated traits have been revealed by genomics and epigenomics, while transcriptomics, proteomics, and immunogenomics have also depicted a more detailed landscape of phenotypes and cell states of immune cells, as well as the roles of key molecules such as Toll-like receptors (TLRs) in promoting autoimmune responses, yielding profound insights for the understanding of SjD. Meanwhile, these diverse data analysis methods offer the researchers impotant tools to further invertigate and understand SjD in the future. The convergence of these modalities supports data-driven disease prediction, refined patient stratification, and identification of therapeutic targets, thereby expanding translational opportunities. Collectively, integrating innovative omics with classical methodologies provides a coherent framework for capturing the pathogenesis of SjD, linking system-wide views to experimental validation, and accelerating the path from pathobiology to precision therapeutics. This review summarizes recent advances in the understanding of the pathogenesis of SjD, lymphomagenesis in SjD, patient stratification and promising targeted therapy, and also outlines future perspectives and challenges to be addressed.]]> Wed, 31 Dec 1969 19:00:00 EST Whole-genome paternal uniparental disomy identified through prenatal single-nucleotide polymorphism-based cell-free DNA screening. Benn P, Hashimoto K, Souter V, Dhamankar R, Xu W, Kijacic D
Ultrasound Obstet Gynecol (Jan 2026)

Prenatal single-nucleotide polymorphism (SNP)-based cell-free DNA (cfDNA) screening can identify genome-wide paternal uniparental disomy (GW-UPDpat), including cases with complete hydatidiform mole with a coexisting fetus (CHMCF), those with placental mesenchymal dysplasia (PMD) and those with a mosaic/chimeric GW-UPDpat syndrome. Our objective was to review laboratory data and pregnancy outcome for SNP-based cfDNA screening tests with results compatible with GW-UPDpat and a normal cell line.]]> Wed, 31 Dec 1969 19:00:00 EST Comparative characterization of chromatin-targeting mechanisms across seven H3K4 methyltransferases in Arabidopsis. Oya S, Uehara S, Watabe H, Juliarni , Kodama Y, Mori S, Osakabe A, Tanaka N, Noyori T, Takahashi M, Nomoto M, Tada Y, Kakutani T, Inagaki S
Plant Commun (Jan 2026)

Methylation of histone H3 at lysine 4 (H3K4me) marks transcribed elements of the eukaryotic genome, and its distribution dynamically changes through developmental stages and in response to environmental factors. These dynamic regulatory changes are achieved by the combinatorial action of H3K4me methyltransferases, with multi-cellular organisms carrying multiple copies of these enzymes. The model plant Arabidopsis has at least seven H3K4 methyltransferase genes. Here, we comparatively analyze the seven H3K4 methyltransferases using epigenomics and biochemical approaches to better understand the mechanisms underlying their target specificity. Our findings, in combination with previous work, show that ATX1 to ATX5 (Trx/Trr-type methyltransferases) localize to loci with distinct sets of chromatin modifications and DNA motifs, which differ among the various ATX proteins. Notably, ATX3 localizes to the binding motifs of ASR3 and RAP2.11 transcriptional factors and directly interacts with these TFs. ATXR7 (Set1-type) and ATXR3 (non-canonical H3K4 methyltransferase) co-localize with the transcriptional machinery, suggesting co-transcriptional mechanisms of action for these enzymes. Interestingly, ATXR3, the major H3K4me3 methyltransferase in Arabidopsis, appears to form a protein complex independent of COMPASS, indicating that the regulatory mechanisms of H3K4me3 have diverged between plants and animals. Our work provides a foundation for understanding the chromatin targeting of H3K4 methyltransferases in plants and highlights significant differences in H3K4me3 regulation between plants and other eukaryotes.]]> Wed, 31 Dec 1969 19:00:00 EST From genes to lifestyle: A multi-dimensional framework for Alzheimer's disease prevention and therapy. Su L, Wang Y
Ageing Res Rev (Jan 2026)

Alzheimer's disease (AD) is a complex neurodegenerative disorder driven by multilayered molecular and cellular mechanisms that cannot be fully elucidated through single-omics approaches. Consequently, large-scale multi-omics integration-encompassing transcriptomics, epigenomics (e.g., methylation), and genetic association studies (GWAS/eQTL/mQTL)-has uncovered critical genetic and epigenetic networks underlying disease risk and progression.Based on these integrative insights, this review emphasized several genes-including KLHL21, SCN2B, ZNF415, and PITRM1-as potential contributors to AD pathogenesis. Notably, single-cell and spatial transcriptomics analyses revealed specific enrichment of these genes in astrocytes, underscoring the pivotal role of this cell type in Aβ clearance, tau propagation, and neuroinflammation. Exercise interventions were shown to selectively modulate the expression of these genes, providing molecular support for the preventive and therapeutic potential of non-pharmacological lifestyle strategies. Drug repurposing analyses using DrugBank have identified promising therapeutic candidates, including FDA-approved agents (e.g., valproic acid, raloxifene, and clomipramine) and naturally derived compounds (e.g., quercetin and fisetin), which may modulate key AD-related pathways. Furthermore, emerging evidence of miRNA-gene regulatory networks suggested an additional layer of post-transcriptional control that may regulate responses to pathological stimuli. Collectively, these integrative insights advocated for a multidimensional precision medicine framework that spans genetic, cellular,network, and lifestyle levels of regulation. This shift from single-target therapeutics to an integrated "gene-cell-network-lifestyle" paradigm open new theoretical and translational avenues for delaying or mitigating AD progression.]]> Wed, 31 Dec 1969 19:00:00 EST