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 Sun, 22 Feb 2026 04:29:30 EST Sun, 22 Feb 2026 04:29:30 EST jirtle@radonc.duke.edu james001@jirtle.com Structural insight into hierarchical DNMT3A autoinhibition and its dysregulation in disease. Lu J, Vig E, Chen J, Gretarsson KH, Khudaverdyan N, Shao Z, Lu C, Chang CA, Song J
Nat Commun (Feb 2026)

DNA methyltransferase DNMT3A-mediated DNA methylation is important for genomic imprinting and transcriptional regulation. However, how the regulatory domains of DNMT3A cooperate with its methyltransferase domain and histone marks to orchestrate genomic methylation remains unclear. Here we report the cryo-EM structure of DNMT3A2 with regulatory factor DNMT3L, revealing an intricate domain interaction underlying multilayered autoinhibition. The PWWP domain interacts with the ADD and methyltransferase domains to block the target recognition domain and the H3K36me2-binding pocket, thereby coupling the H3K36me2 binding with DNMT3A activation, adding a layer of allosteric regulation distinct from the previously characterized ADD-H3K4me0 regulation. Molecular dynamics simulations of the DNMT3A-DNMT3L complex further reveals that relief of DNMT3A autoinhibition involves disengagement of the CpG-recognition loop of the target recognition domain from autoinhibitory interaction, leading to enhanced accessibility of the target recognition domain loop for DNA binding and DNMT3A activation. Importantly, our combined structural, biochemical and genomic methylation analysis demonstrates that disrupting the PWWP-ADD interaction by disease-associated DNMT3A mutations leads to impaired DNMT3A autoinhibition and substrate specificity, providing a potential explanation to aberrant DNA methylation in disease.]]> Wed, 31 Dec 1969 19:00:00 EST Oxidized LDL Induces Pro-Inflammatory Transcriptomic and Epigenomic Responses in Human CD4 T Cells. Brown TA, Chalisey A, Jiang J, O'Callaghan CA
FASEB J (Feb 2026)

Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a key risk factor for coronary artery disease (CAD). The pathogenesis of CAD is multifactorial, driven by heritable and lifestyle-related risk factors. Although CD4 T cells are one of the main cell types in atherosclerotic lesions, their interaction with atherogenic oxidized LDL (ox-LDL) remains poorly understood. Therefore, we sought to characterize the transcriptomic and epigenomic consequences of ox-LDL on activated human CD4 T cells. We find that ox-LDL causes a shift towards a pro-inflammatory, cytokine-producing CD4 T cell transcriptomic state. Concurrently, ox-LDL induces genome-wide changes in chromatin accessibility, notably in promoter regions. By integrating our multiomic data, we identify the NRF1 and SP1 transcription factors as likely mediators of ox-LDL-induced changes in gene expression. In contrast, the influence of AP-1 related factors over CD4 T cell gene expression decreases following ox-LDL stimulation. We leveraged our multiomic data to investigate the disease relevance of ox-LDL exposure, by investigating genomic locations where CAD-associated single nucleotide polymorphisms were found within dynamic ox-LDL-regulated accessible chromatin regions. Together, we demonstrate a disease-relevant role for ox-LDL in atherogenic conditioning of CD4 T cells. Understanding such cell-type specific interactions with CAD risk factors may facilitate the development of targeted therapies for CAD.]]> Wed, 31 Dec 1969 19:00:00 EST A cell type enrichment analysis tool for brain DNA methylation data (CEAM). MÃ¼ller 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 The Role of Non-coding RNAs in Connective Tissue Diseases: Diagnostic and Therapeutic Potential of miRNAs, lncRNAs and circRNAs. Botor M, StÄpieÅ KL, Jankowska K, Thlon M
Mol Diagn Ther (Feb 2026)

Connective tissue diseases (CTDs) are a heterogeneous group of disorders characterized by structural and functional impairment of the extracellular matrix, manifesting primarily as autoimmune, heritable or degenerative conditions such as systemic lupus erythematosus (SLE), osteogenesis imperfecta (OI) and abdominal aortic aneurysm (AAA). In SLE, lupus nephritis remains a leading cause of morbidity and a major determinant of long-term outcomes. Recent advances in transcriptomics and epigenomics have revealed non-coding RNAs (ncRNAs), including microRNA (miRNAs), long non-coding RNA (lncRNAs) and circular RNA (circRNAs), as pivotal regulators of gene expression, immune responses and tissue remodeling. Their tissue-specific expression profiles, molecular stability and involvement in key pathogenic pathways make them promising candidates for diagnostic biomarkers and therapeutic interventions. In this review, we summarize current knowledge of the roles of ncRNAs in CTDs, focusing on their regulatory mechanisms in immune dysregulation, extracellular matrix homeostasis and cell fate determination. Furthermore, we highlight their diagnostic potential in liquid biopsy approaches and discuss therapeutic strategies employing RNA mimics, inhibitors and antisense oligonucleotides. Finally, we address future perspectives, including the integration of multi-omics approaches and targeted delivery systems, which may accelerate the translation of ncRNA-based therapies into clinical practice.]]> Wed, 31 Dec 1969 19:00:00 EST DNA methylation-mediated alterations in Copper(I/II) redox equilibrium underlie lead-induced neurotoxicity. Hu J, Wang WX
Environ Pollut (Apr 2026)

Lead (Pb), a ubiquitous environmental toxin, poses significant risks to central nervous system health, primarily by disrupting essential metal homeostasis in the brain. While epigenetic regulation and proteomic expression are significantly affected by Pb, its specific molecular impact on copper (Cu) redox states remains poorly understood. This study systematically investigated the molecular mechanisms underlying Pb-induced neurotoxicity in SH-SY5Y cells through integrated epigenomics and proteomics analysis. DNA methylation analysis revealed 141,357 differentially methylated regions (DMRs), primarily in CpG sites, with 62.6Â % hypermethylated and 37.4Â % hypomethylated. These DMRs were enriched in genes associated with critical processes such as metal ion binding, cell cycle regulation, and nervous system development. Promoter-specific methylation changes were notably pronounced, impacting pathways linked to neurodegenerative diseases, including Alzheimer's disease. Proteomic analysis identified 740 differentially expressed proteins (DEPs), with 366 upregulated and 374 downregulated in Pb-treated cells. Functional annotation revealed significant enrichment of DEPs in mitochondria, where Pb exposure disrupted processes related to oxidative phosphorylation, ion transport, and transmembrane processes. These proteomic changes aligned with the observed epigenetic modifications, reinforcing the role of Pb in impairing neuronal function via its effects on cellular energy metabolism and metal ion dynamics. Notably, Pb exposure disrupted Cu redox transitions between Cu(I) and Cu(II) as well as glutathione (GSH) activity, underscoring its impact on cellular metal homeostasis regulation and oxidative imbalance. In summary, this study provides a comprehensive view of how Pb exposure alters epigenetic and proteomic landscapes, disrupting key biological processes and pathways essential for neuronal health.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic regulation of serine biosynthesis by PHF8 during neurogenesis. Artes MH, Iacobucci S, Barallobre MJ, Carballeira P, Garcia-Cajide M, PÃ©rez-Venteo A, Padilla N, Viegas BS, DÃaz-VÃ¡squez A, Nacht AS, Vicent GP, ArbonÃ©s ML, de la Cruz X, Nieto M, Agell N, Mauvezin C, MartÃnez-BalbÃ¡s MA
EMBO Rep (Feb 2026)

Progenitor proliferation during neurodevelopment requires tight coordination of epigenetic regulation and metabolism. However, the crosstalk between these processes remains poorly understood. To investigate this, we examine in neural stem cells the role of PHF8, a histone demethylase whose mutations are linked to Siderius-Hamel syndrome, a rare neurodevelopmental disorder. Through an integrated multi-omics approach - combining transcriptomics, epigenomics, and metabolomics - we identify PHF8 as a key driver of the serine biosynthesis pathway, safeguarding the intracellular serine pool essential for neural progenitor proliferation. PHF8 fine-tunes chromatin accessibility at promoters of metabolic genes, ensuring their activation during development. Loss of PHF8 disrupts amino acid metabolism, blocks autophagy, and hinders vesicle formation. Ultimately PHF8 depletion leads to replication defects, DNA damage, and proliferation arrest. In vivo, PHF8 deficiency in mouse embryos halts neurogenesis, progenitor expansion, and neuron generation in the developing brain. These findings identify PHF8 as a key molecular link between chromatin regulation, metabolic control, and neural development, offering new insights into the epigenetic basis of neurodevelopmental and metabolic disorders.]]> Wed, 31 Dec 1969 19:00:00 EST : a computational suite for DNA methylation sequencing data analysis. Loyfer N, Rosenski J, Kaplan T
Life Sci Alliance (Apr 2026)

Next-generation methylation-aware sequencing of DNA sheds light on the fundamental role of methylation in cellular function in health and disease, increasing the number of covered CpG sites from hundreds of thousands in previous array-based approaches to tens of millions across the whole genome. While array-based approaches are limited to single-CpG resolution, next-generation sequencing allows for a more detailed, single-molecule fragment-level analysis; however, existing tools to fully use this capability are not yet well developed. Here, we present , an extensive computational suite tailored for methylation sequencing data. allows fast access and ultracompact anonymized representation of high-throughput methylome data, obtained through various library preparation and sequencing methods, with a custom epiread file format achieving a compression factor of over 100x from the input BAM file. In addition, contains state-of-the-art algorithms for genomic segmentation, biomarker identification, genetic and epigenetic data integration, and more. offers fragment-level analysis and informative visualizations, across multiple genomic regions and samples.]]> Wed, 31 Dec 1969 19:00:00 EST Interpretable data integration for single-cell and spatial multi-omics. Yang C, He Z, Nie Q, Zhang L
Cell Syst (Feb 2026)

Integrating single-cell or spatial transcriptomic and epigenomic data enables scrutinizing the transcriptional regulatory mechanisms controlling cell fate. Current integration methods usually align multi-omics data into a shared latent space but fail to reveal the underlying connections between genes and regulatory elements. The correlation- or regression-based regulatory inference methods cannot dissect different transcriptional regulation codes for cells under different spatial and temporal states. To address both problems, we develop a feature-guided optimal transport (FGOT) method, which simultaneously uncovers cellular heterogeneity and their associated transcriptional regulatory links. FGOT also provides post hoc interpretability for existing integration methods. FGOT is applicable for paired/unpaired single-cell multi-omics data and paired spatial multi-omics data. Benchmarking and validating via histone modification data or three-dimensional (3D) genomics data show good robustness and accuracy in integration and inference of regulatory links. The method allows systematic screening of cell-state and spatial-location-specific regulatory elements in diseases at the single-cell level. A record of this paper's transparent peer review process is included in the supplemental information.]]> Wed, 31 Dec 1969 19:00:00 EST Synergistic integration of clinical and multi-omics data for early MCI diagnosis using an attention-based graph fusion network. Yu S, Zhao J, Ouyang J, Wang X, Kou P, Zhu K, Liu P
J Neurosci Methods (Apr 2026)

Mild cognitive impairment (MCI), a precursor to Alzheimer's disease (AD), requires precise early diagnosis. Single-omics approaches often miss disease complexity, motivating integrative and interpretable solutions.]]> Wed, 31 Dec 1969 19:00:00 EST Melatonin-enabled omics: understanding plant responses to single and combined abiotic stresses for climate-smart agriculture. Raza A, Li Y, Charagh S, Guo C, Zhao M, Hu Z
GM Crops Food (Dec 2026)

Climate change-driven single and combined abiotic stresses pose escalating threats to sustainable, climate-smart agriculture and global food security. Melatonin (MLT, a powerful plant biostimulant) has established noteworthy potential in improving stress tolerance by regulating diverse physiological, biochemical, and molecular responses. Therefore, this review delivers a comprehensive synopsis of MLT-enabled omics responses across genomics, transcriptomics, proteomics, metabolomics, miRNAomics, epigenomics, phenomics, ionomics, and microbiomics levels that collectively regulate plant adaptation to multiple abiotic stresses. We also highlight the crosstalk between these omics layers and the power of integrated multi-omics (panomics) approaches to harness the complex regulatory networks underlying MLT-enabled stress tolerance. Lastly, we argue for translating these omics insights into actionable strategies through advanced genetic engineering and synthetic biology platforms to develop MLT-enabled, stress-smart crop plants.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic Clocks of Biological Aging and Risk of Incident Mild Cognitive Impairment and Dementia: The Women's Health Initiative Memory Study. Nguyen S, Lu AT, Horvath S, Espeland MA, Rapp SR, Maihofer AX, Nievergelt CM, LaCroix AZ, McEvoy LK, Resnick SM, Beckman K, Shadyab AH
Aging Cell (Mar 2026)

Aging is the strongest risk factor for dementia; however, few studies have examined the association of biological aging with incident dementia. We analyzed 6069 cognitively unimpaired women (mean ageâ=â70.0âÂ±â3.8âyears) in the Women's Health Initiative Memory Study to examine the association of accelerated biological aging, measured with second and third-generation epigenetic clocks (AgeAccelPheno and AgeAccelGrim2, and DunedinPACE, respectively) with incident mild cognitive impairment (MCI) and probable dementia. Multivariable Cox proportional hazards models adjusted for age, education, race, ethnicity, smoking, hormone therapy regimen, physical activity, body mass index, and estimated white blood cell counts. For comparison, we also examined first-generation epigenetic clocks (AgeAccelHorvath; AgeAccelHannum). We evaluated effect modification by age, race/ethnicity, hormone therapy regimen, menopause type (natural vs. surgical), and APOE Îµ4 carriage. There were 1307 incident MCI or probable dementia events over a median follow-up of 9.3 (25th percentileâ=â6.1, 75th percentileâ=â16.1) years. The adjusted HRs (95% CI; p-value) for incident MCI/probable dementia per one-standard deviation increment were 1.07 (1.01-1.15; pâ=â0.03) for DunedinPACE, 1.11 (1.02-1.20; pâ=â0.01) for AgeAccelGrim2, and 1.01 (0.95-1.07; pâ=â0.74) for AgeAccelPheno. Only AgeAccelGrim2 remained significant under the Bonferroni-corrected threshold for significance (pâ<â0.02). Other epigenetic clocks were not associated with incident MCI/probable dementia. There was no effect modification in most subgroup analyses (p-interaction â¥â0.05). In this cohort study of older women, accelerated biological aging measured by AgeAccelGrim2 was associated with higher risk of incident MCI/probable dementia. These findings provide evidence linking epigenetic biomarkers of biological aging with MCI and dementia development, independent of chronological age.]]> Wed, 31 Dec 1969 19:00:00 EST Noninvasive diagnosis of colorectal adenoma: The emerging potential of blood-based biomarkers. Qi CY, Wang R, Wang JW, Ye GL, Yang P, Zhou YP
World J Gastroenterol (Feb 2026)

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death globally. Most CRCs arise from colorectal adenomas (CRAs), particularly advanced adenomas, which are recognized as critical precancerous lesions. Early detection and intervention at the adenoma stage are essential for alleviating the global disease burden of CRC. However, conventional screening methods such as colonoscopy are invasive and have poor compliance, underscoring the urgent need for efficient, noninvasive diagnostic alternatives. Blood-based biomarkers have gained substantial attention because of their accessibility, reproducibility, and potential for early detection. Advances in multiomics technologies including proteomics, metabolomics, transcriptomics, and epigenomics have led to the identification of numerous plasma- and serum-derived biomarkers. These include noncoding RNAs (, microRNAs, circular RNAs, PIWI-interacting RNAs), DNA methylation signatures, disease-specific proteins, and metabolic profiles. Moreover, emerging platforms such as liquid biopsy, extracellular vesicle profiling, and machine learning further expand the landscape of early CRA detection. The integration of multiomics data holds promise for substantially increasing the sensitivity and specificity of early adenoma detection, offering a transformative framework for precise CRC screening and risk stratification.]]> Wed, 31 Dec 1969 19:00:00 EST âfolate axis as a modulator of the epigenetic landscape in autoimmune diseases (Review). Navarro-RodrÃguez PM, Bajeca-Serrano RF, Turrubiates-HernÃ¡ndez FJ, Ceja-GÃ¡lvez HR, HernÃ¡ndez-Bello J, HernÃ¡ndez-RamÃrez CO, RamÃrez-de Los Santos S, MuÃ±oz-Valle JF
Int J Mol Med (Mar 2026)

The oneâcarbon metabolism pathway, regulated by the methylenetetrahydrofolate reductase (MTHFR) enzyme, represents a key nexus where genetic predisposition and nutrient status converge to shape the epigenetic landscape of autoimmune diseases. The objective of the present review is to synthesize evidence of how the âfolate axis drives epigenomic patterns in these conditions. One of the main diseases involved is rheumatoid arthritis, where drugânaÃ¯ve patients show Tâcell and synovial hypomethylation with cytokineâdriven DNMT suppression, a process aggravated by reduced folate availability and polymorphisms that constrain Sâadenosylmethionine supply. Similarly, in systemic lupus erythematosus, CD4 T cells exhibit global hypomethylation with an interferonâskewed signature (such as ), associated with impaired activity and a folateâdependent SAM:SAH imbalance that further diminishes DNMT function. Finally, in celiac disease, intestinal differential methylation, including LINEâ1 hypomethylation, is observed, driven by glutenâinduced villous atrophy and folate malabsorption. Overall, impaired oneâcarbon metabolism and âdependent methylation capacity may be key determinants of epigenomic dysfunction underlying autoimmune disease and its clinical severity.17.]]> Wed, 31 Dec 1969 19:00:00 EST Machine Learning for Predicting Stroke Risk Stratification Using Multiomics Data: Systematic Review. Yoo HY, Shin H, Kim EJ, Son YJ
J Med Internet Res (Feb 2026)

Stroke is a complex, multidimensional disorder influenced by interacting inflammatory, immune, coagulation, endothelial, and metabolic pathways. Single-omics approaches seldom capture this complexity, whereas multiomics techniques provide complementary insights but generate high-dimensional and correlated feature spaces. Machine learning (ML) offers strategies to manage these challenges; however, the predictive accuracy and reproducibility of multiomics-based ML models for stroke remain poorly characterized.]]> Wed, 31 Dec 1969 19:00:00 EST Computational methods for spatial multi-omics integration. Geng A, Cui C, Luo Z, Xu J, Meng Y, Cui F, Wei L, Zou Q, Zhang Z
Biotechnol Adv (2026)

The rapid development of spatial multi-omics technologies has enabled the simultaneous acquisition of transcriptomic, proteomic, and epigenomic information from the same tissue section. However, substantial differences in distributional properties, data dimensionality, and noise levels across modalities, together with the inherent sparsity and incompleteness of spatial information, pose major challenges for data integration and modeling. In recent years, deep learning-based spatial multi-omics integration algorithms have emerged rapidly, offering new approaches for constructing unified latent representations and achieving cross-modal fusion. In this review, we systematically summarize existing spatial multi-omics integration methods for the first time, categorizing and comparing them from two perspectives. We not only systematically surveyed the datasets employed by these methods, but also highlighted the key downstream analytical tasks they support, and further summarized the major challenges currently faced in spatial multi-omics integration research. Furthermore, we compare the strengths and limitations of different approaches to assist researchers in selecting appropriate methods more efficiently, thereby advancing the application of spatial multi-omics in uncovering multilayer regulatory mechanisms of tissue microenvironments and disease processes.]]> Wed, 31 Dec 1969 19:00:00 EST OMICs data from Tunisian population: challenges and opportunities in the era of precision medicine. Hkimi C, Yaiche H, Kamoun S, Ben Aissa-Haj J, Boujemaa M, Abdelhak S, Ghedira K, Hamdi Y
Per Med (Feb 2026)

The transition to precision medicine (PM) is revolutionizing healthcare by enabling diagnostics and treatments tailored to individual molecular and genetic profiles, with omics sciences at its core. In Tunisia, growing interest is seen through initiatives such as Personalized Medicine in North Africa (PerMediNA).]]> 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 (Mar 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-2Î± 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 From mammary glands to nutrients: genetic insights into milk compositionâ . AlSulaiti B, Ferguson-Smith AC, Hanin G
Biol Reprod (Feb 2026)

Lactation is a cornerstone of mammalian life, providing nutrient-rich milk that supports offspring growth and development. Breastfeeding offers immediate and long-term benefits for infant and maternal health, shaping life-course health outcomes and reducing disease risks. Milk is a complex and dynamic fluid containing nutrients and bioactive molecules, and its composition is affected by environmental and genetic factors. Research on human milk falls into two primary areas: its biochemistry, which explores milk composition, and epidemiology, which examines the impact of lactation and breastfeeding on health. Together, these fields provide insights into the function of milk components. However, the genetic mechanisms that determine and influence milk composition remain poorly understood. Most findings linking genetics and milk composition have emerged from agricultural studies, where the mechanistic understanding is limited. In-vivo studies focus on mammary gland development, lactation, and cancer mechanisms, yet these interconnected topics are often divided across different research fields. Emerging evidence also suggests a role for genomic imprinting in the regulation of postnatal resource allocation via lactation and milk composition. This review aims to provide a summary of current knowledge on genetic influences affecting milk composition, offering a holistic perspective that unifies mammary gland physiology, milk biochemistry, lactation epidemiology, and genetics.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-epigenome-wide analyses and meta-analysis of child maltreatment in judicial autopsies and intervened children and adolescents. Nishitani S, Fujisawa TX, Takiguchi S, Yao A, Murata K, Hiraoka D, Mizuno Y, Ochiai K, Kawata NYS, Makita K, Saito DN, Mizushima S, Suzuki S, Kurata S, Ishiuchi N, Taniyama D, Nakao N, Namera A, Okazawa H, Nagao M, Tomoda A
Mol Psychiatry (Mar 2026)

Child maltreatment (CM) is associated with adverse physical, psychological, and neurodevelopmental outcomes later in life. Epigenetic modifications, particularly DNA methylation, have been proposed as potential mechanisms underlying these long-term effects. To identify robust CM-associated methylation signatures, we conducted epigenome-wide analyses across three independent cohorts: judicial autopsy cases (CM:11, Controls:7), toddlers shortly after social intervention (CM:36, Controls:49), and adolescents who underwent brain MRI (CM:61, Controls:62). Each cohort was analyzed separately, followed by a meta-analysis to identify common methylation sites associated with CM exposure. The meta-analysis identified four significant CpG sites located within the ATE1, SERPINB9P1, CHST11, and FOXP1 genes. Among these, methylation of FOXP1 was consistently associated with structural brain alterations, including increased gray matter volume (GMV) in the orbitofrontal cortex (OFrC) and middle/posterior cingulate gyrus (MPCG), and decreased GMV in the occipital fusiform gyrus (OFuG). These brain regions are implicated in emotional regulation, memory retrieval, and social cognition, suggesting a potential neurobiological mechanism linking CM to later psychopathology. Furthermore, methylation risk scores (MRS) derived from these four CpGs successfully discriminated individuals who experienced early-life adversity in an independent validation dataset, achieving an area under the receiver operating characteristic curve (AUC) of 0.672, highlighting their potential utility as biomarkers. Gene ontology and pathway analyses revealed enrichment of cholinergic and glutamatergic synaptic transmission pathways, supporting their involvement in traumatic memory formation. Our findings provide novel insights into the epigenetic mechanisms underlying CM and identify potential biomarkers for early detection, prevention, and therapeutic intervention, ultimately contributing to breaking the intergenerational cycle of maltreatment.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetics and Disease Progression in Neuroendocrine Neoplasms. Lobato EC, Lafranchi AF, Freitas-Castro F, Fagundes GFC, Sadikovic B, Lines KE, Almeida MQ
Endocr Rev (Feb 2026)

Epigenetic regulation, including DNA methylation, histone modifications, non-coding RNAs, and higher-order chromatin remodeling, plays a central role in the biology of neuroendocrine neoplasms (NENs). Advances in high-throughput profiling have uncovered epigenetic alterations across pheochromocytomas/paragangliomas (PPGLs), gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), lung neuroendocrine neoplasms (LNENs), medullary thyroid carcinoma (MTC), and pituitary NETs (PitNETs). These alterations converge on pathways governing cell cycle control, telomere maintenance, hypoxia signaling, epithelial-mesenchymal transition, and chromatin architecture. Importantly, epigenetic signatures not only mirror genetic backgrounds (e.g., SDHx, MEN1, ATRX, RET) but also provide independent layers of prognostic and predictive information. Distinct methylation profiles, histone modification patterns, and deregulated miRNA/lncRNA networks have been consistently linked to tumor aggressiveness, metastatic potential, and therapeutic resistance. The clinical translation of these insights is rapidly evolving. Methylation-based classifiers and circulating epigenetic markers are emerging as promising tools for early diagnosis, risk stratification, and longitudinal monitoring. Moreover, epigenetic pathways represent attractive therapeutic targets, with DNA methyltransferase inhibitors, histone deacetylase inhibitors, and RNA-modifying enzyme modulators under active investigation. However, significant challenges remain, including methodological heterogeneity, small or retrospective cohorts, and the limited functional validation of candidate biomarkers. Future priorities include prospective multi-institutional validation, integration of epigenomics with other molecular layers in multidimensional classifiers, and the application of spatial and single-cell approaches to resolve intra-tumoral heterogeneity. Ultimately, epigenetic research has redefined our understanding of NEN pathogenesis and progression, positioning the epigenome as a promising frontier in precision oncology. Through robust validation, epigenetic biomarkers and therapies may transform the clinical management of NENs.]]> Wed, 31 Dec 1969 19:00:00 EST