'; ?> 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, 01 Jun 2023 18:29:01 EDT Thu, 01 Jun 2023 18:29:01 EDT jirtle@radonc.duke.edu james001@jirtle.com Biallelic MGMT loss in a case of IDH-wild-type adult glioblastoma: a case for concurrent epigenomic and molecular karyotype testing. Low JP, Satgunaseelan L, Wright D
Pathology (Jun 2023)

]]> Wed, 31 Dec 1969 19:00:00 EST Patterns, mechanisms, and consequences of homoeologous exchange in allopolyploid angiosperms: a genomic and epigenomic perspective. Deb SK, Edger PP, Pires JC, McKain MR
New Phytol (Jun 2023)

Allopolyploids result from hybridization between different evolutionary lineages coupled with genome doubling. Homoeologous chromosomes (chromosomes with common shared ancestry) may undergo recombination immediately after allopolyploid formation and continue over successive generations. The outcome of this meiotic pairing behavior is dynamic and complex. Homoeologous exchanges (HEs) may lead to the formation of unbalanced gametes, reduced fertility, and selective disadvantage. By contrast, HEs could act as sources of novel evolutionary substrates, shifting the relative dosage of parental gene copies, generating novel phenotypic diversity, and helping the establishment of neo-allopolyploids. However, HE patterns vary among lineages, across generations, and even within individual genomes and chromosomes. The causes and consequences of this variation are not fully understood, though interest in this evolutionary phenomenon has increased in the last decade. Recent technological advances show promise in uncovering the mechanistic basis of HEs. Here, we describe recent observations of the common patterns among allopolyploid angiosperm lineages, underlying genomic and epigenomic features, and consequences of HEs. We identify critical research gaps and discuss future directions with far-reaching implications in understanding allopolyploid evolution and applying them to the development of important phenotypic traits of polyploid crops.]]> Wed, 31 Dec 1969 19:00:00 EST Comparison between indicine and taurine cattle DNA methylation reveals epigenetic variation associated to differences in morphological adaptive traits. Capra E, Lazzari B, Milanesi M, Nogueira GP, Garcia JF, Utsunomiya YT, Ajmone-Marsan P, Stella A
Epigenetics (Dec 2023)

Indicine and taurine subspecies present distinct morphological traits as a consequence of environmental adaptation and artificial selection. Although the two subspecies have been characterized and compared at genome-wide level and at specific loci, their epigenetic diversity has not yet been explored. In this work, Reduced Representation Bisulphite Sequencing (RRBS) profiling of the taurine Angus (A) and indicine Nellore (N) cattle breeds was applied to identify methylation differences between the two subspecies. Genotyping by sequencing (GBS) of the same animals was performed to detect single nucleotide polymorphisms (SNPs) at cytosines in CpG dinucleotides and remove them from the differential methylation analysis. A total of 660,845 methylated cytosines were identified within the CpG context (CpGs) across the 10 animals sequenced (5 N and 5 A). A total of 25,765 of these were differentially methylated (DMCs). Most DMCs clustered in CpG stretches nearby genes involved in cellular and anatomical structure morphogenesis. Also, sequences flanking DMC were enriched in SNPs compared to all other CpGs, either methylated or unmethylated in the two subspecies. Our data suggest a contribution of epigenetics to the regulation and divergence of anatomical morphogenesis in the two subspecies relevant for cattle evolution and sub-species differentiation and adaptation.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomic profiling of isolated blood cell types reveals highly specific B cell smoking signatures and links to disease risk. Wang X, Campbell MR, Cho HY, Pittman GS, Martos SN, Bell DA
Clin Epigenetics (May 2023)

Tobacco smoking alters the DNA methylation profiles of immune cells which may underpin some of the pathogenesis of smoking-associated diseases. To link smoking-driven epigenetic effects in specific immune cell types with disease risk, we isolated six leukocyte subtypes, CD14+ monocytes, CD15+ granulocytes, CD19+ B cells, CD4+ T cells, CD8+ T cells, and CD56+ natural killer cells, from whole blood of 67 healthy adult smokers and 74 nonsmokers for epigenome-wide association study (EWAS) using Illumina 450k and EPIC methylation arrays.]]> Wed, 31 Dec 1969 19:00:00 EST Uncertainty quantification of reference-based cellular deconvolution algorithms. Vellame DS, Shireby G, MacCalman A, Dempster EL, Burrage J, Gorrie-Stone T, Schalkwyk LS, Mill J, Hannon E
Epigenetics (Dec 2023)

The majority of epigenetic epidemiology studies to date have generated genome-wide profiles from bulk tissues (e.g., whole blood) however these are vulnerable to confounding from variation in cellular composition. Proxies for cellular composition can be mathematically derived from the bulk tissue profiles using a deconvolution algorithm; however, there is no method to assess the validity of these estimates for a dataset where the true cellular proportions are unknown. In this study, we describe, validate and characterize a sample level accuracy metric for derived cellular heterogeneity variables. The CETYGO score captures the deviation between a sample's DNA methylation profile and its expected profile given the estimated cellular proportions and cell type reference profiles. We demonstrate that the CETYGO score consistently distinguishes inaccurate and incomplete deconvolutions when applied to reconstructed whole blood profiles. By applying our novel metric to >6,300 empirical whole blood profiles, we find that estimating accurate cellular composition is influenced by both technical and biological variation. In particular, we show that when using a common reference panel for whole blood, less accurate estimates are generated for females, neonates, older individuals and smokers. Our results highlight the utility of a metric to assess the accuracy of cellular deconvolution, and describe how it can enhance studies of DNA methylation that are reliant on statistical proxies for cellular heterogeneity. To facilitate incorporating our methodology into existing pipelines, we have made it freely available as an R package (https://github.com/ds420/CETYGO).]]> Wed, 31 Dec 1969 19:00:00 EST Peripheral Ischemia Imprints Epigenetic Changes in Hematopoietic Stem Cells to Propagate Inflammation and Atherosclerosis. Coppin E, Zhang X, Ohayon L, Johny E, Dasari A, Zheng KH, Stiekema L, Cifuentes-Pagano E, Pagano PJ, Chaparala S, Stroes ES, Dutta P
Arterioscler Thromb Vasc Biol (Jun 2023)

Peripheral ischemia caused by peripheral artery disease is associated with systemic inflammation, which may aggravate underlying comorbidities such as atherosclerosis and heart failure. However, the mechanisms of increased inflammation and inflammatory cell production in patients with peripheral artery disease remain poorly understood.]]> Wed, 31 Dec 1969 19:00:00 EST Inter and transgenerational impact of H3K4 methylation in neuronal homeostasis. Abay-Nørgaard S, Tapia MC, Zeijdner M, Kim JH, Won KJ, Porse B, Salcini AE
Life Sci Alliance (Aug 2023)

Epigenetic marks and associated traits can be transmitted for one or more generations, phenomena known respectively as inter- or transgenerational epigenetic inheritance. It remains unknown if genetically and conditionally induced aberrant epigenetic states can influence the development of the nervous system across generations. Here, we show, using as a model system, that alteration of H3K4me3 levels in the parental generation, caused by genetic manipulation or changes in parental conditions, has, respectively, trans- and intergenerational effects on H3K4 methylome, transcriptome, and nervous system development. Thus, our study reveals the relevance of H3K4me3 transmission and maintenance in preventing long-lasting deleterious effects in nervous system homeostasis.]]> Wed, 31 Dec 1969 19:00:00 EST Genomic and epigenomic determinants of heat stress-induced transcriptional memory in Arabidopsis. Kappel C, Friedrich T, Oberkofler V, Jiang L, Crawford T, Lenhard M, Bäurle I
Genome Biol (May 2023)

Transcriptional regulation is a key aspect of environmental stress responses. Heat stress induces transcriptional memory, i.e., sustained induction or enhanced re-induction of transcription, that allows plants to respond more efficiently to a recurrent HS. In light of more frequent temperature extremes due to climate change, improving heat tolerance in crop plants is an important breeding goal. However, not all heat stress-inducible genes show transcriptional memory, and it is unclear what distinguishes memory from non-memory genes. To address this issue and understand the genome and epigenome architecture of transcriptional memory after heat stress, we identify the global target genes of two key memory heat shock transcription factors, HSFA2 and HSFA3, using time course ChIP-seq.]]> Wed, 31 Dec 1969 19:00:00 EST High-throughput methods for the analysis of transcription factors and chromatin modifications: Low input, single cell and spatial genomic technologies. Salma M, Andrieu-Soler C, Deleuze V, Soler E
Blood Cells Mol Dis (Jul 2023)

Genome-wide analysis of transcription factors and epigenomic features is instrumental to shed light on DNA-templated regulatory processes such as transcription, cellular differentiation or to monitor cellular responses to environmental cues. Two decades of technological developments have led to a rich set of approaches progressively pushing the limits of epigenetic profiling towards single cells. More recently, disruptive technologies using innovative biochemistry came into play. Assays such as CUT&RUN, CUT&Tag and variations thereof show considerable potential to survey multiple TFs or histone modifications in parallel from a single experiment and in native conditions. These are in the path to become the dominant assays for genome-wide analysis of TFs and chromatin modifications in bulk, single-cell, and spatial genomic applications. The principles together with pros and cons are discussed.]]> Wed, 31 Dec 1969 19:00:00 EST A case of KAT6A syndrome with a newly discovered mutation in the gene, mainly manifested as bone marrow failure syndrome. Ai Q, Jiang L, Chen Y, Yao X, Yin J, Chen S
Hematology (Dec 2023)

The clinical and genetic characteristics of a child with inherited bone marrow failure syndrome as prominent clinical manifestations and special facial features were analyzed, and the etiology and mechanism were explored in, combination with clinical practice. Blood samples and clinical information were collected separately from the proband and their biological parents. The pathogenic variant was verified using next-generation sequencing technology screening, and the candidate variable sites were confirmed by using Sanger sequencing among all members of the family. A heterozygous nonsense mutation in exon 17 of (NM_006766), c.4177G > T (p.E1393*) predicted to cause truncation within the acidic domain of the protein was identified. Pedigree analysis did not reveal any variation in this locus between the proband's father and mother. No report of this pathogenic variant was found in a literature search of domestic and foreign databases, indicating that it is a newly discovered mutation. According to the guidelines of the American College of Medical Genetics, the variation was preliminarily determined to be a pathogenic. The newly discovered heterozygous mutation in may be the cause of the disease in this child. Additionally, inherited bone marrow failure syndrome is a prominent manifestation. This study not only provides us with an in-depth understanding of this rare syndrome but also deepens our understanding of the function of .]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomic machinery regulating pediatric AML: Clonal expansion mechanisms, therapies, and future perspectives. Chianese U, Papulino C, Megchelenbrink W, Tambaro FP, Ciardiello F, Benedetti R, Altucci L
Semin Cancer Biol (Jul 2023)

Acute myeloid leukemia (AML) is a heterogeneous disease with a genetic, epigenetic, and transcriptional etiology mainly presenting somatic and germline abnormalities. AML incidence rises with age but can also occur during childhood. Pediatric AML (pAML) accounts for 15-20% of all pediatric leukemias and differs considerably from adult AML. Next-generation sequencing technologies have enabled the research community to "paint" the genomic and epigenomic landscape in order to identify pathology-associated mutations and other prognostic biomarkers in pAML. Although current treatments have improved the prognosis for pAML, chemoresistance, recurrence, and refractory disease remain major challenges. In particular, pAML relapse is commonly caused by leukemia stem cells that resist therapy. Marked patient-to-patient heterogeneity is likely the primary reason why the same treatment is successful for some patients but, at best, only partially effective for others. Accumulating evidence indicates that patient-specific clonal composition impinges significantly on cellular processes, such as gene regulation and metabolism. Although our understanding of metabolism in pAML is still in its infancy, greater insights into these processes and their (epigenetic) modulation may pave the way toward novel treatment options. In this review, we summarize current knowledge on the function of genetic and epigenetic (mis)regulation in pAML, including metabolic features observed in the disease. Specifically, we describe how (epi)genetic machinery can affect chromatin status during hematopoiesis, leading to an altered metabolic profile, and focus on the potential value of targeting epigenetic abnormalities in precision and combination therapy for pAML. We also discuss the possibility of using alternative epidrug-based therapeutic approaches that are already in clinical practice, either alone as adjuvant treatments and/or in combination with other drugs.]]> Wed, 31 Dec 1969 19:00:00 EST Effect of epigenetic activating of Dlk1-Dio3 imprinted cluster on miR-370 expression due to folate deficiency during nerve development. Chang S, Min J, Lu X, Zhang Q, Shangguan S, Zhang T, Wang L
J Nutr Biochem (Jun 2023)

Proper Dlk1-Dio3 imprinting plays a critical role in embryogenesis, and folic acid deficiency may affect the imprinting of this locus through epigenetic regulation. However, whether and how folic acid directly impacts the imprinting status of Dlk1-Dio3 to affect neural development remain unclear. Here, we found decreased IG-DMR (intergenic -differentially methylated regions) methylation in the folate-deficient encephalocele in humans, suggesting that abnormal Dlk1-Dio3 imprinting status is related to neural tube defects (NTDs) caused by folate deficiency. Similar results were obtained with folate-deficient embryonic stem cells. By miRNA chip analysis, folic acid deficiency led to changes in multiple miRNAs, including the upregulation of 15 miRNAs located in the Dlk1-Dio3 locus. Real-time PCR confirmed that seven of these miRNAs were upregulated, especially miR-370. In contrast to normal embryonic development, in which expression of miR-370 is highest at E9.5, the abnormally high and sustained expression of miRNA-370 in folate-deficient E13.5 embryos may contribute to NTDs. In addition, we found that DNMT3A (de novo DNA methyltransferases 3A) is a direct target gene of miR-370 in neural cells, and DNMT3A participates in the role of miR-370 in inhibiting cell migration. Finally, in the folate-deficient mouse model, Dlk1-Dio3 epigenetic activation was found in fetal brain tissue, along with the upregulation of miR-370 and the downregulation of DNMT3A. Collectively, our findings demonstrate a pivotal role of folate in the epigenetic regulation of Dlk1-Dio3 imprinting during neurogenesis, revealing an elegant mechanism for the activation of Dlk1-Dio3 locus miRNAs in folic acid deficiency.]]> Wed, 31 Dec 1969 19:00:00 EST Unveiling the epigenomic mechanisms of acquired platinum-resistance in high-grade serous ovarian cancer. Silva R, Glennon K, Metoudi M, Moran B, Salta S, Slattery K, Treacy A, Martin T, Shaw J, Doran P, Lynch L, Jeronimo C, Perry AS, Brennan DJ
Int J Cancer (Jul 2023)

Resistance to platinum-based chemotherapy is the major cause of death from high-grade serous ovarian cancer (HGSOC). We hypothesise that detection of specific DNA methylation changes may predict platinum resistance in HGSOC. Using a publicly available "discovery" dataset we examined epigenomic and transcriptomic alterations between primary platinum-sensitive (n = 32) and recurrent acquired drug resistant HGSOC (n = 28) and identified several genes involved in immune and chemoresistance-related pathways. Validation via high-resolution melt analysis of these findings, in cell lines and HGSOC tumours, demonstrated the most consistent changes were observed in three of the genes: APOBEC3A, NKAPL and PDCD1. Plasma samples from an independent HGSOC cohort (n = 17) were analysed using droplet digital PCR. Hypermethylation of NKAPL was detected in 46% and hypomethylation of APOBEC3A in 69% of plasma samples taken from women with relapsed HGSOC (n = 13), with no alterations identified in disease-free patients (n = 4). Following these results, and using a CRISPR-Cas9 approach, we were also able to demonstrate that in vitro NKAPL promoter demethylation increased platinum sensitivity by 15%. Overall, this study demonstrates the importance of aberrant methylation, especially of the NKAPL gene, in acquired platinum resistance in HGSOC.]]> Wed, 31 Dec 1969 19:00:00 EST Towards artificial intelligence to multi-omics characterization of tumor heterogeneity in esophageal cancer. Li J, Li L, You P, Wei Y, Xu B
Semin Cancer Biol (Jun 2023)

Esophageal cancer is a unique and complex heterogeneous malignancy, with substantial tumor heterogeneity: at the cellular levels, tumors are composed of tumor and stromal cellular components; at the genetic levels, they comprise genetically distinct tumor clones; at the phenotypic levels, cells in distinct microenvironmental niches acquire diverse phenotypic features. This heterogeneity affects almost every process of esophageal cancer progression from onset to metastases and recurrence, etc. Intertumoral and intratumoral heterogeneity are major obstacles in the treatment of esophageal cancer, but also offer the potential to manipulate the heterogeneity themselves as a new therapeutic strategy. The high-dimensional, multi-faceted characterization of genomics, epigenomics, transcriptomics, proteomics, metabonomics, etc. of esophageal cancer has opened novel horizons for dissecting tumor heterogeneity. Artificial intelligence especially machine learning and deep learning algorithms, are able to make decisive interpretations of data from multi-omics layers. To date, artificial intelligence has emerged as a promising computational tool for analyzing and dissecting esophageal patient-specific multi-omics data. This review provides a comprehensive review of tumor heterogeneity from a multi-omics perspective. Especially, we discuss the novel techniques single-cell sequencing and spatial transcriptomics, which have revolutionized our understanding of the cell compositions of esophageal cancer and allowed us to determine novel cell types. We focus on the latest advances in artificial intelligence in integrating multi-omics data of esophageal cancer. Artificial intelligence-based multi-omics data integration computational tools exert a key role in tumor heterogeneity assessment, which will potentially boost the development of precision oncology in esophageal cancer.]]> Wed, 31 Dec 1969 19:00:00 EST How does the body know how old it is? Mitteldorf J
Exp Gerontol (Jun 2023)

Based on the ideas of R. A. Fisher, neoDarwinism came to dominate evolutionary science in the first half of the wentieth entury, and within that perspective aging could never be an evolved adaptation. But as the genetic and epigenetic mechanisms of aging came to be elucidated in many species, the signature of an adaptation became clear. Simultaneously, evolutionary theorists were proposing diverse selective mechanisms that might account for adaptations that are beneficial to the community, even as they imposed a fitness cost on the individual. Epigenetic conceptions of aging gained currency with the development of methylation clocks beginning in 2013. The idea that aging is an epigenetic program has propitious implications for the feasibility of medical rejuvenation. It should be easier to intervene in the body's age-related signaling, or even to reprogram the body's epigenetics, compared to brute-force repair of all the physical and chemical damage that accrues with age. The upstream clock mechanism(s) that control the timing of growth, development, and aging remain obscure. I propose that because of the need of all biological systems to be homeostatic, we should expect that aging is controlled by multiple, independent timekeepers. A single point of intervention may be available in the signaling that these clocks use to coordinate information about the age of the body. This may be a way of understanding the successes to date of plasma-based rejuvenation.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic inhibition of lncRNA GMDS-AS1 by methyltransferase ESET promoted cell viability and metastasis of hepatocellular carcinoma. Huang J, Zhong T, Li G, Wang S, Qin R
Clin Transl Oncol (Jun 2023)

Long noncoding RNA (lncRNAs) GMDS-AS1 has been reported as a tumor regulator in tumor growth and metastasis, but its effect in hepatocellular carcinoma (HCC) remains unclear. ESET, a histone H3K9 methyl-transferase, is involved in epigenomic regulation of tumor progression in multiple cancers. However, the correlation between ESET and lncRNA in HCC is less reported.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic control is involved in molecular dialogue in plant-microbe symbiosis. Zimmermann SD, Gaillard I
New Phytol (Jun 2023)

]]> Wed, 31 Dec 1969 19:00:00 EST Network models of chromatin structure. Pancaldi V
Curr Opin Genet Dev (May 2023)

Increasing numbers of datasets and experimental assays that capture the organization of chromatin inside the nucleus warrant an effort to develop tools to visualize and analyze these structures. Alongside polymer physics or constraint-based modeling, network theory approaches to describe 3D epigenome organization have gained in popularity. Representing genomic regions as nodes in a network enables visualization of 1D epigenomics datasets in the context of chromatin structure maps, while network theory metrics can be used to describe 3D epigenome organization and dynamics. In this review, we summarize the most salient applications of network theory to the study of chromatin contact maps, demonstrating its potential in revealing epigenomic patterns and relating them to cellular phenotypes.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomes get personal. Koch L
Nat Rev Genet (Jun 2023)

]]> Wed, 31 Dec 1969 19:00:00 EST The impact of local genomic properties on the evolutionary fate of genes. Hara Y, Kuraku S
Elife (May 2023)

Functionally indispensable genes are likely to be retained and otherwise to be lost during evolution. This evolutionary fate of a gene can also be affected by factors independent of gene dispensability, including the mutability of genomic positions, but such features have not been examined well. To uncover the genomic features associated with gene loss, we investigated the characteristics of genomic regions where genes have been independently lost in multiple lineages. With a comprehensive scan of gene phylogenies of vertebrates with a careful inspection of evolutionary gene losses, we identified 813 human genes whose orthologs were lost in multiple mammalian lineages: designated 'elusive genes.' These elusive genes were located in genomic regions with rapid nucleotide substitution, high GC content, and high gene density. A comparison of the orthologous regions of such elusive genes across vertebrates revealed that these features had been established before the radiation of the extant vertebrates approximately 500 million years ago. The association of human elusive genes with transcriptomic and epigenomic characteristics illuminated that the genomic regions containing such genes were subject to repressive transcriptional regulation. Thus, the heterogeneous genomic features driving gene fates toward loss have been in place and may sometimes have relaxed the functional indispensability of such genes. This study sheds light on the complex interplay between gene function and local genomic properties in shaping gene evolution that has persisted since the vertebrate ancestor.]]> Wed, 31 Dec 1969 19:00:00 EST