'; ?> 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, 06 Mar 2025 17:58:28 EST Thu, 06 Mar 2025 17:58:28 EST jirtle@radonc.duke.edu james001@jirtle.com Epigenomic landscape of the human dorsal root ganglion: sex differences and transcriptional regulation of nociceptive genes. Franco-Enzástiga Ãš, Inturi NN, Natarajan K, Mwirigi JM, Mazhar K, Schlachetzki JCM, Schumacher M, Price TJ
Pain (Mar 2025)

Cell states are influenced by the regulation of gene expression orchestrated by transcription factors capable of binding to accessible DNA regions. To uncover if sex differences exist in chromatin accessibility in the human dorsal root ganglion (hDRG), where nociceptive neurons innervating the body are found, we performed bulk and spatial assays for transposase-accessible chromatin technology followed by sequencing (ATAC-seq) from organ donors without a history of chronic pain. Using bulk ATAC-seq, we detected abundant sex differences in the hDRG. In women, differentially accessible regions (DARs) mapped mostly to the X chromosome, whereas in men, they mapped to autosomal genes. Hormone-responsive transcription factor binding motifs such as EGR1/3 were abundant within DARs in women, while JUN, FOS, and other activating protein 1 factor motifs were enriched in men, suggesting a higher activation state of cells compared with women. These observations were consistent with spatial ATAC-seq data. Furthermore, we validated that EGR1 expression is biased to female hDRG using RNAscope. In neurons, spatial ATAC-seq revealed higher chromatin accessibility in GABAergic, glutamatergic, and interferon-related genes in women and in Ca2+-signaling-related genes in men. Strikingly, XIST, responsible for inactivating 1 X chromosome by compacting it and maintaining at the periphery of the nucleus, was found to be highly dispersed in female neuronal nuclei. This is likely related to the higher chromatin accessibility in X in female hDRG neurons observed using both ATAC-seq approaches. We have documented baseline epigenomic sex differences in the hDRG which provide important descriptive information to test future hypotheses.]]> Wed, 31 Dec 1969 19:00:00 EST DNA Methylation and Target Gene Expression in Fatty Liver Progression From Simple Steatosis to Advanced Fibrosis. Li J, Liu X, Tran TT, Lee M, Tsai RYL
Liver Int (Mar 2025)

Metabolic dysfunction-associated steatotic liver diseases (MASLD), also known as non-alcoholic fatty liver diseases (NAFLD), have become a leading risk factor for hepatocellular carcinoma (HCC) in Western countries. NAFLD progresses from simple steatosis to HCC, with advanced liver fibrosis (ALF) and metabolic dysfunction-associated steatohepatitis (MASH) or non-alcoholic steatohepatitis (NASH) representing the two preceding high-risk stages.]]> Wed, 31 Dec 1969 19:00:00 EST Long non coding RNA function in epigenetic memory with a particular emphasis on genomic imprinting and X chromosome inactivation. Le LTT
Gene (Apr 2025)

Cells preserve and convey certain gene expression patterns to their progeny through the mechanism called epigenetic memory. Epigenetic memory, encoded by epigenetic markers and components, determines germline inheritance, genomic imprinting, and X chromosome inactivation. First discovered long non coding RNAs were implicated in genomic imprinting and X-inactivation and these two phenomena clearly demonstrate the role of lncRNAs in epigenetic memory regulation. Undoubtedly, lncRNAs are well-suited for regulating genes in close proximity at imprinted loci. Due to prolonged association with the transcription site, lncRNAs are able to guide chromatin modifiers to certain locations, thereby enabling accurate temporal and spatial regulation. Nevertheless, the current state of knowledge regarding lncRNA biology and imprinting processes is still in its nascent phase. Herein, we provide a synopsis of recent scientific advancements to enhance our comprehension of lncRNAs and their functions in epigenetic memory, with a particular emphasis on genomic imprinting and X chromosome inactivation, thus gaining a deeper understanding of the role of lncRNAs in epigenetic regulatory networks.]]> Wed, 31 Dec 1969 19:00:00 EST A menu for microbes: unraveling appetite regulation and weight dynamics through the microbiota-brain connection across the lifespan. Ribeiro G, Schellekens H, Cuesta-Marti C, Maneschy I, Ismael S, Cuevas-Sierra A, Martínez JA, Silvestre MP, Marques C, Moreira-Rosário A, Faria A, Moreno LA, Calhau C
Am J Physiol Gastrointest Liver Physiol (Mar 2025)

Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut-microbiota-targeted approaches such as pre-, pro-, post-, and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is ) to provide an overview of the role of the microbiota-gut-brain axis in appetite regulation across the lifespan and ) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.]]> Wed, 31 Dec 1969 19:00:00 EST Rare Causes and Differential Diagnosis in Patients With Silver-Russell Syndrome. Braga BL, da Cunha Scalco R, Homma TK, Freire BL, Cellin LP, Canton APM, Lerario AM, de Assis Funari MF, de Souza V, Bertola DR, Malaquias AC, Mendonca BB, de Lima Jorge AA
Clin Genet (Apr 2025)

Silver-Russell syndrome (SRS) is an imprinting disorder mainly characterized by pre- and postnatal growth restriction. Most SRS cases are due to 11p15.5 loss of methylation (11p15.5 LOM) or maternal uniparental disomy of chromosome 7 [UPD(7)mat], but several patients remain molecularly undiagnosed. This study describes the molecular investigation of children with a clinical diagnosis or suspicion of SRS at a tertiary center specialized in growth disorders. Thirty-nine patients were evaluated with multiplex ligation-dependent probe amplification, chromosomal microarray and/or massively parallel sequencing. The most common result was 11p15.5 LOM (n = 17; 43.5%), followed by UPD(7)mat (n = 2; 5.1%). Additionally, we found maternal duplications of the imprinting centers in 11p15.5 (n = 2; 5.1%), and genetic defects in SRS-causing genes (IGF2 and HMGA2) (n = 3; 7.7%; two mutations and one deletion). Alternative molecular diagnoses included UPD(14)mat (n = 1; 2,6%), UPD(20)mat (n = 1;2,6%), copy number variants (n = 2; 5.1%), and mutations in genes associated with other growth disorders (n = 4; 10.3%), leading to diagnoses of Temple syndrome, Mulchandani-Bhoj-Conlin syndrome, IGF-1 resistance (IGF1R), Bloom syndrome (BLM), Gabriele-De Vries syndrome (YY1), Intellectual developmental disorder autosomal dominant 50 with behavioral abnormalities (NAA15), and Intellectual developmental disorder 64 (ZNF292). These findings underscore the importance of establishing the molecular diagnosis of SRS and its differential diagnoses to guide appropriate management and genetic counseling.]]> Wed, 31 Dec 1969 19:00:00 EST Mediation of Social Determinants and Hypertension by Epigenetic Age in CARDIA. Szeto MD, Ning H, Pedamallu H, Zheng Y, Schneper L, Joyce B, Kim K, Kershaw KN, Reges O, Hou L, Allen NB, Notterman DA, Lloyd-Jones DM
Hypertension (Mar 2025)

]]> Wed, 31 Dec 1969 19:00:00 EST Extensive epigenomic dysregulation is a hallmark of homologous recombination deficiency in triple-negative breast cancer. Chen Y, Salas LA, Marotti JD, Jenkins NP, Cheng C, Miller TW, Kettenbach AN, Christensen BC
Int J Cancer (Mar 2025)

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with substantial disease heterogeneity, limited treatment options, and dismal clinical outcomes. Some TNBCs display homologous recombination deficiency (HRD), a phenotype with elevated genomic burden and worse prognosis if left untreated but chemotherapeutic sensitivity. While the molecular landscape of TNBC is distinct from other breast cancer subtypes, the TNBC-specific link between HRD and epigenome-wide methylation has not been established. This study reports two independent cohorts of TNBC tumors (n = 32 and n = 58) with HRD and epigenomic landscapes measured by the Multiplex Ligation-dependent Probe Amplification assay and the Illumina MethylationEPIC arrays, respectively. Genome-wide copy number and methylation alterations were significantly higher in HRD (all p <.05). Methylation of genome-wide repeat element Alu and transcriptional regulatory regions were significantly lower in HRD (all p <.05). An age-adjusted epigenome-wide association study of the continuous HRD probability scores revealed significant loci (all FDR <0.05) that were depleted from the CpG-rich "island" regions often seen in gene promoters but enriched in the CpG-poor "open sea" regions localized to gene enhancers. The significant loci implicated well-known candidate genes involved in the epithelial-to-mesenchymal transition, Wnt signaling, and DNA damage response. Supervised machine learning of HRD with nucleotide-specific methylation as the input enabled clinically relevant tumor stratification. Taken together, this study provides novel biological and translational insights into HRD in TNBCs.]]> Wed, 31 Dec 1969 19:00:00 EST The eighth annual US DOHAD meeting: promising approaches in epigenetics research of early life exposures. Non AL
Epigenomics (Mar 2025)

The U.S. Developmental Origins of Health and Disease (DOHaD) meeting is an annual conference of primarily U.S. scientists who study early life programming of health and disease. The eighth annual symposium, entitled "Exploring Translational DOHaD Science: From Cells to Communities" was held at the Rizzo Conference Center in Chapel Hill, North Carolina, from October 14 to 16, 2024. The meeting was organized by US-DOHaD President Danielle Christifano and Vice President Kaela Varberg, and other Society Council Members. This year's meeting had record attendance, with 158 attendees from diverse disciplines, and featured 10 keynote speakers, 11 platform talks, and 84 poster presentations. Four major topics were covered: 1) Early nutrition and developmental outcomes, 2) Prenatal origins of child health, 3) Developmental impacts of toxicant exposures, and 4) Metabolic origins of health. Overall, the presented research highlighted the value of studying epigenetic effects of dietary and toxic exposures early in life. Various strategies emerged to address challenges facing the field, such as harnessing the power of nationwide longitudinal birth cohorts, new methods to integrate epigenetic and environmental data across various levels, and the emerging potential of organoids to identify the causal impact of early life exposures.]]> Wed, 31 Dec 1969 19:00:00 EST The interplay between epigenomic and transcriptomic variation during ecotype divergence in stickleback. Luo M, Zhao J, Merilä J, Barrett RDH, Guo B, Hu J
BMC Biol (Mar 2025)

Populations colonizing contrasting environments are likely to undergo adaptive divergence and evolve ecotypes with locally adapted phenotypes. While diverse molecular mechanisms underlying ecotype divergence have been identified, less is known about their interplay and degree of divergence.]]> 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 Epigenomic pathways from racism to preterm birth: secondary analysis of the Nulliparous Pregnancy Outcomes Study: monitoring Mothers-to-be (nuMoM2b) cohort study in the USA to examine how DNA methylation mediates the relationship between multilevel racism and preterm birth in black women: a study protocol. Barcelona V, Ray M, Zhao Y, Samari G, Wu H, Reho P, McNeil R, Reddy UM
BMJ Open (Mar 2025)

Preterm birth is a significant contributor to pregnancy-related morbidity and mortality, particularly affecting black women. Racism is a key driver of perinatal inequities, but mechanisms remain unclear. Epigenomics research offers promise in understanding how environmental exposures, including racism, influence gene expression and adverse pregnancy outcomes. We present our study protocol describing how we will investigate the interactive effects of individual- and structural-level racism on preterm birth within and across black and white women, characterise the blood-based methylome of black pregnant women and identify whether DNA methylation mediates the association between multilevel racism and preterm birth in black women.]]> Wed, 31 Dec 1969 19:00:00 EST Family study of bipolar disorder with comorbid anxiety disorder points to with possible role of parent-of-origin effect. Maki H, Sakai N, Kataoka M, Fujii K, Kageyama Y, Hayama T, Matsuo K, Nishioka M, Kato T
PCN Rep (Mar 2025)

The aim of this study was to provide new insights into the genetics of bipolar disorder (BD) by analyzing BD comorbid with anxiety disorders.]]> Wed, 31 Dec 1969 19:00:00 EST Novel Approach to Overcome Osimertinib Resistance Using Bromodomain and Extra-Terminal Domain Inhibitors. Miyashita Y, Tajima K, Izumi K, Matsumoto N, Hayakawa D, Nakamura IT, Katayama I, Wibowo A, Matsuda H, Winardi W, Amien BR, Mitsuishi Y, Takahashi F, Nakamura K, Uchibori K, Yanagitani N, Hayashi T, Takamochi K, Suzuki K, Katayama R, Takahashi K
Cancer Sci (Mar 2025)

Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, is the first-line therapy for lung cancer harboring EGFR mutations. The mechanisms underlying osimertinib resistance are diverse, with approximately half remaining unknown. Epigenetic dysregulation is implicated in drug resistance; however, the mechanisms remain unclear. Therefore, we investigated epigenetic involvement in osimertinib resistance and its therapeutic potential. We established osimertinib-resistant cells and used an assay for transposase-accessible chromatin using sequencing to evaluate chromatin accessibility, finding significant changes post-resistance. Combining the assay for transposase-accessible chromatin and RNA sequencing data, we identified FGF1 as a resistance-related gene regulated by histone modifications. FGF1 induced osimertinib resistance, and its suppression attenuated resistance. Bromodomain and extra-terminal domain inhibitors combined with osimertinib overcame osimertinib resistance by reducing FGF1 expression. Increased FGF1 expression was observed in osimertinib-resistant clinical samples. This combination therapy was effective in cell lines and mouse xenograft models. These results suggest targeting histone modifications using bromodomain and extra-terminal domain inhibitors as a novel approach to overcoming osimertinib resistance.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomic Changes in Ostrinia Moths Under Elevated Pupal and Adult Temperature. Velikaneye BA, Kozak GM
Mol Ecol (Mar 2025)

Epigenetic changes in the methylation of DNA may occur in response to environmental stressors, including warming climates. DNA methylation may also play an important role in regulating gene expression during both male and female reproduction in many insect species. However, it is currently unknown how DNA methylation shifts when individuals are reproducing under warmer temperatures. We exposed European corn borer moths (Ostrinia nubilalis) to heat during the pupal and adult life stages then investigated changes in DNA methylation across the genome using enzymatic methyl-seq (EM-seq). We compared methylation patterns in reproductive males and females exposed to heat (28°C) to those that experienced an ambient temperature (23°C). We found that heat exposure led to a small but significant increase in the percentage of methylated CpG sites throughout the genome in both sexes. However, DNA methylation rates were higher in females and differential methylation following heat exposure localised to unique regions in each sex. In males, methylation shifted within genes belonging to pathways including Hippo signalling, ubiquitin-mediated proteolysis, DNA damage repair and spermatogenesis. In females, differential methylation occurred in genes related to histone modification and oogenesis. Our results suggest that DNA methylation patterns respond to moderate heat exposure in Lepidoptera and provide insight into epigenetic responses to heatwaves, suggesting novel pathways that may be involved in responding to heat stress during metamorphosis and reproduction.]]> Wed, 31 Dec 1969 19:00:00 EST Activation of Imprinted Gene Promotes Cardiac Fibrosis After Ischemic Injury. Kou S, Lu Z, Deng D, Ye M, Sui Y, Qin L, Feng T, Jiang Z, Meng J, Lin CP, Li X, Liu C, Tang J, Zhang H
Circulation (Mar 2025)

Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments. (paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood.]]> Wed, 31 Dec 1969 19:00:00 EST Heritable dysregulation of DNA methylation may underlie the diabetogenic effects of paternal preconception exposure to inorganic arsenic in C57BL/6J mice. Hartwell HJ, Shang B, Douillet C, Bousquet AG, Liu T, Zou F, Ideraabdullah F, Stýblo M, Fry RC
Toxicol Appl Pharmacol (Mar 2025)

Chronic exposure to inorganic arsenic (iAs) has been linked with the development of diabetes mellitus (DM). We recently showed that parental exposure to iAs (200 ppb) prior to mating was associated with diabetic phenotypes in offspring and altered gene expression in parents and offspring. The goal of the present study was to determine if DNA methylation underlies the differential gene expression in the livers of offspring. DNA methylation was assessed in paternal (G0) sperm and livers of their offspring (G1) using a genome wide DNA methylation array. We found that iAs exposure significantly altered CpG methylation (p < 0.05) in 54.3 %, 49.4 %, and 63.7 % of the differentially expressed genes in G0 sperm, G1 female livers, and G1 male livers, respectively. Importantly, a subset of differentially methylated CpG sites were shared across generations. Sensitivity analyses (FDR < 0.1) of imprinted and DM-associated genes revealed differential methylation of 74 imprinted genes and 100 DM-associated genes in the livers of G1 males. These male-specific results are intriguing given the prior findings of diabetic phenotypes found exclusively in male offspring from parents exposed to iAs. In summary, these data demonstrate that heritable changes in DNA methylation through the paternal germline may underlie the diabetogenic effects of preconception iAs exposure.]]> Wed, 31 Dec 1969 19:00:00 EST Hao-Fountain syndrome protein USP7 controls neuronal differentiation via BCOR-ncPRC1.1. Wolf van der Meer J, Larue A, van der Knaap JA, Chalkley GE, Sijm A, Beikmohammadi L, Kozhevnikova EN, van der Vaart A, Tilly BC, Bezstarosti K, Dekkers DHW, Doff WAS, van de Wetering-Tieleman PJ, Lanko K, Barakat TS, Allertz T, van Haren J, Demmers JAA, Atlasi Y, Verrijzer CP
Genes Dev (Mar 2025)

Pathogenic variants in the ubiquitin-specific protease 7 () gene cause a neurodevelopmental disorder called Hao-Fountain syndrome. However, it remains unclear which of USP7's pleiotropic functions are relevant for neurodevelopment. Here, we present a combination of quantitative proteomics, transcriptomics, and epigenomics to define the USP7 regulatory circuitry during neuronal differentiation. USP7 activity is required for the transcriptional programs that direct both the differentiation of embryonic stem cells into neural stem cells and the neuronal differentiation of SH-SY5Y neuroblastoma cells. USP7 controls the dosage of the Polycomb monubiquitylated histone H2A lysine 119 (H2AK119ub1) ubiquitin ligase complexes ncPRC1.1 and ncPRC1.6. Loss-of-function experiments revealed that BCOR-ncPRC1.1, but not ncPRC1.6, is a key effector of USP7 during neuronal differentiation. Indeed, BCOR-ncPRC1.1 mediates a major portion of USP7-dependent gene regulation during this process. Besides providing a detailed map of the USP7 regulome during neurodifferentiation, our results suggest that USP7- and ncPRC1.1-associated neurodevelopmental disorders involve dysregulation of a shared epigenetic network.]]> Wed, 31 Dec 1969 19:00:00 EST EpiMapper: A new tool for analyzing high-throughput sequencing from CUT&Tag. Dragland JS, Liu G, Nilsen HL, Böttcher Y, Wang J
Comput Biol Med (Mar 2025)

Since the invention of next-generation sequencing, new methods have been developed to understand the regulation of gene expression through epigenetic markers. Among these, CUT&Tag (Cleavage Under Targets and Tagmentation) analysis has emerged as an efficient epigenomic profiling technique with low input requirements, high sensitivity, and low background signals. Although wet-lab techniques are available, data analysis remains challenging for scientists without expert-level computational skills. Therefore, we developed EpiMapper, a new Python package that simplifies the data analysis of CUT&Tag sequencing and similar techniques, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) or ChIP-seq (chromatin immunoprecipitation [ChIP] assays with sequencing), and allows biomedical scientists to easily interpret the results. This new package includes every necessary step, from quality control to annotation and differential peak analysis. In particular, EpiMapper has improved functionality (e.g., reproducibility assessment) compared to previous analysis protocols and visualization plots and provides new features, such as genome annotation and differential peak analysis. Using three case studies, two on CUT&Tag and one on ATAC-seq data, the EpiMapper Python package successfully reproduced previous results.]]> Wed, 31 Dec 1969 19:00:00 EST Late-Onset Progressive Osseous Heteroplasia: 2 Unrelated Cases and Use of Positron Emission Tomography for Diagnosis. Pham MT, Mahan JD, Shah SH, Estes SI, Kaler SG
JCEM Case Rep (Mar 2025)

Progressive osseous heteroplasia (POH) is a rare autosomal-dominant hereditary bone disorder caused by inactivating pathogenic variants in . POH is characterized by progressive cutaneous ossification and heterotopic ossification in skeletal muscles and subdermal connective tissues. Understanding of the natural history and phenotypic heterogeneity of the illness is incomplete. We report 2 affected male subjects with a milder than usual clinical course, highlight their clinical presentations and molecular correlates, and propose sodium F-fluorine positron emission tomography (PET) scanning as a sensitive technique for POH diagnosis and management.]]> Wed, 31 Dec 1969 19:00:00 EST Genetics of Prader-Willi and Angelman syndromes: 2024 update. Godler DE, Singh D, Butler MG
Curr Opin Psychiatry (Mar 2025)

Prader-Willi (PWS) and Angelman (AS) syndromes arise from errors in 15q11-q13 imprinting. This review describes recent advances in genomics and how these expand our understanding of these rare disorders, guiding treatment strategies to improve patient outcomes.]]> Wed, 31 Dec 1969 19:00:00 EST