'; ?> 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 Sat, 28 Jun 2025 07:08:51 EDT Sat, 28 Jun 2025 07:08:51 EDT jirtle@radonc.duke.edu james001@jirtle.com Multi-omics in colorectal cancer liver metastasis: applications and research advances. Zhou K, Yang C, Li Y
Cancer Biol Med (Jun 2025)

Colorectal cancer (CRC) is a common malignant tumor with a high mortality rate worldwide. Advanced CRC often leads to liver metastasis, which has a poor prognosis, highlighting the need to investigate the underlying mechanisms. Omics, encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics, enables comprehensive molecular analysis of cells and tissues. Tumor-omics research has advanced rapidly, with growing attention on CRC-related omics. However, systematic reviews on omics research specific to colorectal cancer liver metastasis (CRLM) are limited. This review summarizes the current status and progress of multi-omics research on CRLM and discusses the application of multi-omics technologies in basic research and the significant clinical implications.]]> 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 The myoblast methylome: multiple types of associations with chromatin and transcription. Sen S, Lacey M, Baribault C, Ponnaluri VKC, Esteve PO, Ehrlich KC, Meletta M, Pradhan S, Ehrlich M
Epigenetics (Dec 2025)

Epigenetic changes are implicated in development, repair, and physiology of postnatal skeletal muscle (SkM). We generated methylomes for human myoblasts (SkM progenitor cells) and determined myoblast differentially methylated regions (DMRs) for comparison to the epigenomics and transcriptomics of diverse cell types. Analyses were from global genomic and single-gene perspectives and included reporter gene assays. One atypical finding was the association of promoter-adjacent hypermethylation in myoblasts with transcription turn-on, but at downmodulated levels, for certain genes (., and ). In contrast, brain-specific was in repressed chromatin and silent in most cell types but linked to hypermethylated DMRs specifically in myoblasts. The -linked DMRs might be needed because of the overlapping or nearby binding of myogenic differentiation protein 1 (MYOD). We found genome-wide overlap of DMRs with MYOD or CCCTC-binding factor (CTCF) binding sites in myoblasts that is consistent with the importance of MYOD, as well as CTCF, in organizing myoblast transcription-enhancing chromatin interactions. We also observed some gene upregulation correlated with a special association of regional DNA hypomethylation with H3K36me3, H3K27ac, and H3K4me1 enrichment. Our study highlights unusual relationships between epigenetics and gene expression that illustrate the interplay between DNA methylation and chromatin epigenetics in the regulation of transcription.]]> Wed, 31 Dec 1969 19:00:00 EST NKX2-5 congenital heart disease mutations show diverse loss and gain of epigenomic, biochemical and chromatin search functions underpinning pathogenicity. Ward AO, Schonrock N, McCann AJ, Phanor SK, Kock KH, Kurland JV, Wu F, Murray NJ, Walshe J, Alankarage D, Dunwoodie SL, Meunier FA, Francois M, Bulyk ML, Ramialison M, Harvey RP
bioRxiv (Jun 2025)

Congenital heart defects (CHD) occur in ∼1% of live births, with both inherited and acquired mutations and environmental factors known to contribute to causation. However, network perturbations and epigenetic changes in CHD remain poorly characterised. We report an integrated functional-epigenomics approach to understanding CHD, focusing on the cardiac homeodomain (HD) family transcription factor NKX2-5, mutations in which cause diverse congenital heart structural and conduction defects. We selected twelve NKX2-5 CHD-associated variants affecting different residue classes - DNA base-contacting, backbone-contacting, helix-stabilizing residues of the homeodomain, and those affecting other conserved protein:protein interaction (PPI) domains. In HL-1 cardiomyocytes, we profiled DNA targets of NKX2-5 wild type (WT) and variant proteins genome-wide using DamID, their DNA binding affinity and specificity using comprehensive protein binding microarrays, and PPI with known NKX2-5 cofactors using yeast 2-hybrid assay. We also undertook deep profiling of chromatin search and binding dynamics using single molecule tracking. Variants showed highly diverse but also class-specific behaviours with a range of severities. All variants failed to bind many WT targets but retained binding to a subset of core cardiomyocyte-related WT NKX2-5 targets, as well as hundreds of unique "off-targets", in part via a regulatory logic that included changes to DNA binding site specificity, homodimerization and lost or enhanced cofactor interactions. All variants tested showed altered chromatin search functions. Our data suggest that complex residue-by-residue scale epigenomic, biochemical and chromatin search perturbations, involving both loss- and gain-of-function, contribute to CHD phenotypes. These findings may inform precision molecular therapeutic approaches in patients with CHD.]]> Wed, 31 Dec 1969 19:00:00 EST Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis. Martin CL, Chen J, D'Alessio AS, Ward-Caviness CK, Ye A, Lodge EK, Ghastine L, Dhingra R, Jima DD, Murphy SK, Hoyo C
Epigenetics (Dec 2025)

Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery. Models for the epigenome-wide and regional analyses were adjusted for maternal age, race/ethnicity, education, smoking, cell-type composition, and offspring sex. Genetic influence and gene expression enrichment were assessed using methylation quantitative trait loci (mQTLs) and expression quantitative trait methylation (eQTMs) analyses. Functional enrichment was determined using Gene Ontology and KEGG databases. We did not find evidence of epigenome-wide associations between prenatal neighborhood crime exposure and DNAm; however, we identified nine differentially methylated regions (DMRs) comprising 51 CpG sites associated with neighborhood crime. CpG sites within significant differentially methylated regions were associated with mQTLs at birth and eQTMs upon further examination. KEGG analysis identified a significant Th1 and Th2 cell differentiation pathway. Our results suggest potential links between prenatal neighborhood crime exposure and offspring DNAm; however, additional research is needed in larger cohorts across wider geographic areas to confirm our results.]]> Wed, 31 Dec 1969 19:00:00 EST How do threatened plant species with low genetic diversity respond to environmental stress? Insights from comparative conservation epigenomics and phenotypic plasticity. Williams BR, Miller AJ, Edwards CE
Mol Ecol Resour (Jul 2025)

Many threatened plants have low genetic diversity, which may reduce their capacity for genetically based adaptation, increasing their extinction risk. Non-genetic variation (e.g. epigenomic modifications such as DNA methylation) and plasticity may facilitate the persistence of threatened plants, yet are rarely incorporated into conservation assessments. We present a case study investigating variation and plasticity in DNA methylation and phenotypic traits in four genetically depauperate species of Leavenworthia (Brassicaceae), including one widespread species and one asexual, threatened species. We grew individuals from several maternal lines and populations per species in contrasting watering treatments, measured phenotypic traits and analysed DNA methylation using whole-genome bisulphite sequencing. We addressed four questions: (1) How do patterns of DNA methylation differ within and among species? (2) Within species, how do phenotypic traits and patterns of DNA methylation vary in response to drought? (3) Does variation in DNA methylation correspond to phenotypic variation? (4) What are the implications for conservation? We found that taxa were epigenomically distinct and that each species exhibited variation in DNA methylation among populations that could be relevant for conservation. Within species, the DNA methylation response to environmental stress corresponded to its phenotypic response. Species differed in their DNA methylation and phenotypic responses to environmental stress, with the extent of plasticity possibly related to species geographic range size. We also found phenotypic and DNA methylation variation in the asexual, threatened species that may be relevant for conservation. Our results suggest that variation in DNA methylation may promote the persistence of genetically depauperate threatened plants, highlighting its potential as a novel conservation target to reduce extinction risk.]]> Wed, 31 Dec 1969 19:00:00 EST use capsules, transporters, mobile genetic elements, and other evolutionary adaptations to survive antibiotics exposure in the absence of resistance genes. Mmatli M, Mbelle NM, Fourie B, Osei Sekyere J
Virulence (Dec 2025)

Whole-genome sequencing, transcriptomic profiling, and epigenomic analyses were performed. Phenotypic assays were used to evaluate the effects of various inhibitors on antibiotic susceptibility, while bioinformatic pipelines were used to characterize resistance determinants, virulence factors, and mobile genetic elements (MGEs).]]> Wed, 31 Dec 1969 19:00:00 EST Thymically imprinted heterogeneity results in differential Treg induction and stability of effector identity. Pennock ND, Qian Y, Ishihara K, Nakamura Y, Cross E, Sakaguchi S, White JT
Cell Rep (Jun 2025)

Thymic selection predisposes naive T cells to particular outcomes when challenged later with cognate antigen, whether the antigen is self or foreign. This suggests that there is an inherent heterogeneity of functioning among T cells within the naive population (both CD4 and CD8), and that each T cell, as part of its thymic development, is given a certain "programming" that will affect its eventual fate decisions. In this project, we looked at the primary effects of this thymic imprinting on the conversion of naive CD4 T cells into Tregs. Furthermore, using an induced-Treg-reporter system, we examine the impact of thymic imprinted heterogeneity on effector functionality and identity stability. We report that naive T cell differential responsivity to cytokines leads to the observed difference in Treg induction and that the Tregs induced from T cells of different self-affinities maintain a heterogeneity of effector function and identity.]]> 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 and are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation. Daskeviciute D, Sainty B, Chappell-Maor L, Bone C, Russell S, Iglesias-Platas I, Arnaud P, Monteagudo-Sánchez A, Greenberg MVC, Chen K, Manerao-Azua A, Perez de Nanclares G, Lartey J, Monk D
Epigenetics (Dec 2025)

Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, and , both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.]]> Wed, 31 Dec 1969 19:00:00 EST Multigenerational exposure to DEHP drives dysregulation of imprinted gene Snurf to impair decidualization. Tan L, Gao R, Su Y, Zhang Y, Geng Y, Liu Q, Ma Y, Chen X, Li F, He J
J Hazard Mater (Aug 2025)

Phthalate-induced female reproductive health issues, particularly those related to di (2-ethylhexyl) phthalate (DEHP), are growing global concerns. Although most studies have focused on single-generation exposure, studies on prolonged DEHP exposure across multiple generations are limited. This study assessed the effects of multigenerational DEHP exposure on endometrial decidualization, which is crucial for embryo implantation. The results showed that sustained DEHP exposure over three generations exacerbated decidualization injury and led to adverse pregnancy outcomes. RNA sequencing revealed upregulation of the imprinted gene Snurf in the decidua, with changes that may not depend on alterations in DNA methylation. Knockdown of Snurf significantly alleviated in vitro decidualization deficiency induced by mono(2-ethylhexyl) phthalate (MEHP), the biologically active metabolite of DEHP. Proteomic analysis and the AlphaFold 3 algorithm indicated that Stn1 is a downstream target of Snurf, with silencing Stn1 resensitizing Snurf-knockdown stromal cells to MEHP. Human decidual stromal cells (hDSCs) from healthy participants showed sensitivity to MEHP, with the inhibition of decidualization. Epidemiological data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) indicated a positive association between DEHP exposure and female infertility. This study highlighted the cumulative toxic effects of multigenerational DEHP exposure on female reproduction and revealed the contribution of imprinted genes.]]> 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 Fertile androgenetic mice generated by targeted epigenetic editing of imprinting control regions. Wei Y, Yue T, Wang Y, Yang Y
Proc Natl Acad Sci U S A (Jul 2025)

Each new mammalian life begins with the fusion of an oocyte and a sperm to produce a fertilized egg containing two sets of genomes, one from the mother and one from the father. Androgenesis, a way for producing offspring solely from male genetic material, is limited in mammals, presumably due to barriers arising from genomic imprinting, an epigenetic mechanism leading to monoallelic gene expression. Here, we report adult mammalian offspring derived from the genetic material of two sperm cells. These mice, which we refer to as androgenetic mice, were produced via targeted DNA methylation editing of seven imprinting control regions (ICRs) through CRISPR-based epigenome engineering. Two sperm cells were injected into an enucleated oocyte to form putatively diploid embryos. Allele-specific epigenetic editing was achieved by injecting guide RNAs with protospacer adjacent motif (PAM) sequences designed to match one allele but not the other. The birth of androgenetic mice that were able to develop to adulthood demonstrates that mammalian androgenesis is achievable by targeted epigenetic remodeling of a few defined ICRs.]]> Wed, 31 Dec 1969 19:00:00 EST Generation of human-induced pluripotent stem cells from a patient with Beckwith-Wiedemann syndrome. Tang M, Lei J, Shao C, Zhou W, Xiong M, Huang M, Huang C, Wang F, Liu J, Li J, Xu X
Hum Cell (Jun 2025)

Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder mainly caused by an imprinting abnormality in the chromosome 11p15.5 region. It is rare and sporadic with unclear etiology and pathogenesis. We identified a family with a clustering of BWS cases arising from methylation abnormality of IC1 region. An induced pluripotent stem-cell line (BWS iPSC) was generated from peripheral blood mononuclear cells (PBMCs) of one affected family member using a non-integrating reprogramming method. This cell line could be further differentiated into multiple lineages, enabling us to determine the relationship of the expression of abnormal imprinting genes in BWS to cellular phenotypes, thus elucidating the pathogenic mechanisms of BWS. In future, the multi-lineage cells can be used to test various innovative therapies, providing conceptual validation for the treatment of BWS.]]> 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 (Jul 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 The roles of maternal one-carbon metabolism and placental imprinted gene expression in placental development and somatic growth in a longitudinal birth cohort. Gutherz OR, Li Q, Deyssenroth M, Wainwright H, Jacobson JL, Meintjes EM, Chen J, Jacobson SW, Carter RC
Placenta (Jun 2025)

One-carbon nutrients and imprinted genes both play critical roles in placental development and somatic growth. We aimed to examine (1) the impact of maternal one-carbon nutrition on placental imprinted gene expression, placental development, and infant growth and (2) interactions between one-carbon nutrients and imprinted genes in placental development and infant growth.]]> Wed, 31 Dec 1969 19:00:00 EST Advances and applications of multiomics technologies in precision diagnosis and treatment for gastric cancer. Shen K, Hu C, Zhang Y, Cheng X, Xu Z, Pan S
Biochim Biophys Acta Rev Cancer (Jul 2025)

Gastric cancer (GC), one of the most prevalent malignancies worldwide, is distinguished by extensive genetic and phenotypic heterogeneity, posing persistent challenges to conventional diagnostic and therapeutic strategies. The significant global burden of GC highlights an urgent need to unravel its complex underlying mechanisms, discover novel diagnostic and prognostic biomarkers, and develop more effective therapeutic interventions. In this context, this review comprehensively examines the transformative roles of cutting-edge technologies, including radiomics, pathomics, genomics, transcriptomics, epigenomics, proteomics, and metabolomics, in advancing precision diagnosis and treatment for GC. Multiomics data analysis not only deepens our understanding of GC pathogenesis and molecular subtypes but also identifies promising biomarkers, facilitating the creation of tailored therapeutic approaches. Additionally, integrating multiomics approaches holds immense potential for elucidating drug resistance mechanisms, predicting patient outcomes, and uncovering novel therapeutic targets, thereby laying a robust foundation for precision medicine in the comprehensive management of GC.]]> Wed, 31 Dec 1969 19:00:00 EST Combined Multiomics Analysis Reveals the Role of Methylation and miRNA-Targeted in Polycystic Ovary Syndrome. Ding Y, Huang L, He M, Zhang F, Jiang Y, Kang Y
Reprod Med Biol (2025)

Polycystic ovary syndrome (PCOS) is an endocrine syndrome that afflicts women of childbearing age, whose specific pathogenesis is unknown. Combined multiomics analysis on it is still lacking. The purpose of this study was to use combined multiomics analyses to learn about the development of PCOS.]]> Wed, 31 Dec 1969 19:00:00 EST Histone modifications as molecular drivers of cardiac aging: Metabolic alterations, epigenetic mechanisms, and emerging therapeutic strategies. Alrumaihi F, Al-Doaiss AA, Ullah F, Alwanian WM, Alharbi HO, Alassaf FA, Alfifi SM, Alshabrmi FM, Aba Alkhay FF, Alatawi EA
Curr Probl Cardiol (Jul 2025)

Cardiac aging represents a complex pathophysiological process characterized by progressive metabolic recombination and functional dedifferentiation of cardiac cellular components. Despite advancements in cardiovascular medicine, a critical research gap persists in understanding the precise epigenetic mechanisms that drive age-related cardiac dysfunction. This comprehensive review elucidates the pivotal role of histone modifications-including methylation, acetylation, and phosphorylation-in orchestrating the molecular landscape of cardiac aging. Significant gaps remain in our understanding of site-specific histone modification impacts on cardiac function, the intricate crosstalk between different histone marks, and their integration with metabolic alterations that characterize the aging myocardium. Current evidence reveals a dynamic epigenetic signature in aged cardiac tissue, typically featuring increased transcriptional activation markers alongside decreased repressive marks, though context-dependent variations exist. This review explores how histone modifications influence critical pathways governing mitochondrial dysfunction, DNA damage repair, inflammation, and fibrosis in aging hearts. Innovative therapeutic approaches targeting specific histone-modifying enzymes promise to mitigate age-related cardiac deterioration, potentially revolutionizing treatment paradigms for cardiovascular diseases in aging populations. Addressing these knowledge gaps requires multidimensional approaches that integrate epigenomics with functional assessment of cardiac performance.]]> Wed, 31 Dec 1969 19:00:00 EST Insights into tissue- and cell type-specific effects of Grb10 on pig skeletal muscle growth by multi-omics analysis. Li M, Liu H, Lu T, Li S, Zhou X, Miao H, Zhang Y, Peng C, Chen K, He J, Yin Y, Zhao P, Han X
Sci China Life Sci (Jun 2025)

Domestic pigs are shaped by artificial and natural selection into obese and lean types that are closely related to muscle tissue. However, the key genes and regulatory mechanisms behind these developments remain largely unknown. Here, we pinpoint GRB10 specificity in muscle tissue and cells between obese and lean pigs by combining genomics, transcriptomics, epigenomics, and single-cell transcriptomics. GRB10 shows notable differences in divergent selection on haplotype blocks and expression levels between obese and lean pig breeds, with its expression profiles varying significantly by tissue and development stage. Notably, we identify a muscle-specific promoter of GRB10 and its transcription factor KLF15. This TF-promoter binding is verified by dual luciferase and chromatin immunoprecipitation (ChIP) assays, and is suggested to be conserved in humans. Single-nucleus RNA sequencing further highlights differential expression patterns of GRB10 between obese and lean pig breeds across various cell types. Type IIa myonuclei and TTN FAPs, which are more predominant in lean pigs, play a crucial role in myofibril assembly and muscle tissue development. These findings offer insights into the regulatory mechanisms controlling muscle growth. They highlight the tissue- and cell type-specific effects of GRB10 on muscle heterogeneity, which has potential applications in livestock breeding and human obesity research.]]> Wed, 31 Dec 1969 19:00:00 EST