'; ?> 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, 18 Apr 2021 23:43:30 EDT Sun, 18 Apr 2021 23:43:30 EDT jirtle@radonc.duke.edu james001@jirtle.com Ovulation Induction Changes Epigenetic Marks of Imprinting Genes in Mice Fetus Organs. Oveisi A, Vahdati A, Shahhoseini M, Favaedi R, Maroufizadeh S, Movaghar B
Cell J (Apr 2021)

Genomic imprinting is an epigenetic phenomenon that plays a critical role in normal development of embryo. Using exogenous hormones during assisted reproductive technology (ART) can change an organism hormonal profile and subsequently affect epigenetic events. Ovarian stimulation changes gene expression and epigenetic pattern of imprinted genes in the organs of mouse fetus.]]> Wed, 31 Dec 1969 19:00:00 EST DeepDRK: a deep learning framework for drug repurposing through kernel-based multi-omics integration. Wang Y, Yang Y, Chen S, Wang J
Brief Bioinform (Apr 2021)

Recent pharmacogenomic studies that generate sequencing data coupled with pharmacological characteristics for patient-derived cancer cell lines led to large amounts of multi-omics data for precision cancer medicine. Among various obstacles hindering clinical translation, lacking effective methods for multimodal and multisource data integration is becoming a bottleneck. Here we proposed DeepDRK, a machine learning framework for deciphering drug response through kernel-based data integration. To transfer information among different drugs and cancer types, we trained deep neural networks on more than 20 000 pan-cancer cell line-anticancer drug pairs. These pairs were characterized by kernel-based similarity matrices integrating multisource and multi-omics data including genomics, transcriptomics, epigenomics, chemical properties of compounds and known drug-target interactions. Applied to benchmark cancer cell line datasets, our model surpassed previous approaches with higher accuracy and better robustness. Then we applied our model on newly established patient-derived cancer cell lines and achieved satisfactory performance with AUC of 0.84 and AUPRC of 0.77. Moreover, DeepDRK was used to predict clinical response of cancer patients. Notably, the prediction of DeepDRK correlated well with clinical outcome of patients and revealed multiple drug repurposing candidates. In sum, DeepDRK provided a computational method to predict drug response of cancer cells from integrating pharmacogenomic datasets, offering an alternative way to prioritize repurposing drugs in precision cancer treatment. The DeepDRK is freely available via https://github.com/wangyc82/DeepDRK.]]> Wed, 31 Dec 1969 19:00:00 EST Role of histone deacetylase Sirt3 in the development and regression of atherosclerosis. Liu Y, Shen X, Pang M, Sun Z, Qian Y, Xue W, Wang Z, Li L
Life Sci (May 2021)

Atherosclerosis (AS) is the most common cause of death in cardiovascular diseases and poses severe challenges to human life and safety. Epigenetics plays a vital role in every single link of AS. Whereas, how epigenetics regulates its development and regression is still unknown. Sirt3, a recognized histone deacetylase, having been reported to be involved in other acylation processes in recent years, is broadening its role in epigenetic modifications. Sirt3 is an important factor in the normal physiology of blood vessels through deacetylation of mitochondrial proteins and participates in various metabolic activities. Besides, medical research targeting Sirt3 is in full swing as well. This review combining histone deacetylase Sirt3 with AS, aims to clarify the latest progress in the significant role of Sirt3 in the development and regression of AS and to provide a novel prospect for a new regulatory factor and potential intervention target for AS.]]> Wed, 31 Dec 1969 19:00:00 EST New diagnostic molecular markers and biomarkers in odontogenic tumors. Farshbaf A, Zare R, Mohajertehran F, Mohtasham N
Mol Biol Rep (Apr 2021)

Odontogenic tumors comprised of complex heterogeneous lesions that diverse from harmatomas to malignant tumors with different behavior and histology. The etiology of odontogenic tumors is not exactly determined and pathologists deal with challenges in diagnosis of odontogenic tumors because they are rare and obtained experiences are difficult to evaluate. In this study, we describe immunohistochemical and molecular markers in diagnosis of odontogenic tumors besides advanced diagnostic technique. Immunohistochemical features of odontogenic tumors beside the clinical features and radiological finding can help us to determine the correct diagnosis. Although these markers are neither specific nor sensitive enough, but analysis of gene expression provides definitive confirmation of diagnosis. In addition, "-omics" technology detected specific molecular alternation associated with etiology such as genomics, epigenomics, transcriptomics, proteomics and metabolomics. The post transcriptional events such as DNA methylation and chromatin remodeling by histone modification affect the changes in epigenome. Furthermore, non-coding RNAs like micro-RNAs, long noncoding RNA (lncRNA) and small non-coding RNA (snoRNA) play regulatory role and impact odontogenesis. Molecular marker propose their potential role in etiopathogenesis of odontogenic tumors and suitable candidate in diagnostic, prognostic and therapeutic approaches in addition to patient management. For future evaluations, organoid represents in vitro tumor model-study for tumor behavior, metastasis and invasion, drug screening, immunotherapy, clinical trial, hallmarks association with prognosis and evolution of personalized anti-cancer therapy. Moreover, organoid biobank help us to check genetic profile. We think more investigation and studies are needed to gain these knowledges that can shift therapeutic approaches to target therapy.]]> Wed, 31 Dec 1969 19:00:00 EST Decoding regulatory structures and features from epigenomics profiles: A Roadmap-ENCODE Variational Auto-Encoder (RE-VAE) model. Hu R, Pei G, Jia P, Zhao Z
Methods (05 2021)

The development of chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing (ChIP-seq) technologies has promoted generation of large-scale epigenomics data, providing us unprecedented opportunities to explore the landscape of epigenomic profiles at scales across both histone marks and tissue types. In addition to many tools directly for data analysis, advanced computational approaches, such as deep learning, have recently become promising to deeply mine the data structures and identify important regulators from complex functional genomics data. We implemented a neural network framework, a Variational Auto-Encoder (VAE) model, to explore the epigenomic data from the Roadmap Epigenomics Project and the Encyclopedia of DNA Elements (ENCODE) project. Our model is applied to 935 reference samples, covering 28 tissues and 12 histone marks. We used the enhancer and promoter regions as the annotation features and ChIP-seq signal values in these regions as the feature values. Through a parameter sweep process, we identified the suitable hyperparameter values and built a VAE model to represent the epigenomics data and to further explore the biological regulation. The resultant Roadmap-ENCODE VAE (RE-VAE) model contained data compression and feature representation. Using the compressed data in the latent space, we found that the majority of histone marks were well clustered but not for tissues or cell types. Tissue or cell specificity was observed only in some histone marks (e.g., H3K4me3 and H3K27ac) and could be characterized when the number of tissue samples is large (e.g., blood and brain). In blood, the contributive regions and genes identified by RE-VAE model were confirmed by tissue-specificity enrichment analysis with an independent tissue expression panel. Finally, we demonstrated that RE-VAE model could detect cancer cell lines with similar epigenomics profiles. In conclusion, we introduced and implemented a VAE model to represent large-scale epigenomics data. The model could be used to explore classifications of histone modifications and tissue/cell specificity and to classify new data with unknown sources.]]> Wed, 31 Dec 1969 19:00:00 EST The DNA cytosine-5-methyltransferase 3 (DNMT3) involved in regulation of CgIL-17 expression in the immune response of oyster Crassostrea gigas. Zhao Q, Wang W, Li JX, Yuan P, Liu Y, Li Y, Wang L, Song L
Dev Comp Immunol (Apr 2021)

DNA methyltransferase, a key enzyme mediating DNA methylation, is involved in numerous processes including genomic imprinting, X chromosome inactivation, transposable element suppression, and immune defense in vertebrates. In the present study, a DNA cytosine-5-methyltransferase 3 was identified from oyster Crassostrea gigas (designed as CgDNMT3). There were a PWWP domain, a PHD domain and a DNA-methylase domain in the deduced amino acid sequences of CgDNMT3, and the conserved motifs I, IV, VI, Ⅷ, IX and X were identified in its C-terminal catalytic DNA-methylase domain. The mRNA transcripts of CgDNMT3 were detected in haemocytes, mantle, gill, adductor muscle, digestive gland and labial palp, with higher expression level in haemocytes (6.54 folds of those in gill, p < 0.01). The expression level of CgDNMT3 mRNA in haemocytes increased significantly after LPS primed (2.87 folds of that in control group, p < 0.05) in vitro or Vibrio splendidus challenging (1.94 folds of that in control group, p < 0.05) in vivo. Immunocytochemical analysis revealed that CgDNMT3 protein was distributed mainly in cytoplasm and partial in nucleus of oyster haemocytes. After CgDNMT3 was transfected and expressed in HEK293T cells, the DNA 5-methylcytosine (5-mc) level in the transfected group was significantly increased, which was 1.22 folds (p < 0.05) of the pcDNA-3.1 group (p < 0.05). The expressions of oyster CgIL17-1, CgIL17-2 and CgIL17-5 in haemocytes increased (13.05 folds, 4.78 folds and 9.41 folds of that in control group, respectively) at 12 h after V. splendidus challenging, but the increase were significantly inhibited when the oysters were pre-treated with DNA methyltransferase inhibitor 5-Azacytidine, which were 9 folds, 1.93 folds and 3.22 folds of that in control group, respectively. These results collectively suggested that CgDNMT3 was a conserved member of DNA methyltransferase 3 family in oysters, and participated in regulating the expression of cytokines during immune response.]]> Wed, 31 Dec 1969 19:00:00 EST Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. Pauler FM, Hudson QJ, Laukoter S, Hippenmeyer S
Neurochem Int (May 2021)

Genomic imprinting is an epigenetic mechanism that results in parental allele-specific expression of ~1% of all genes in mouse and human. Imprinted genes are key developmental regulators and play pivotal roles in many biological processes such as nutrient transfer from the mother to offspring and neuronal development. Imprinted genes are also involved in human disease, including neurodevelopmental disorders, and often occur in clusters that are regulated by a common imprint control region (ICR). In extra-embryonic tissues ICRs can act over large distances, with the largest surrounding Igf2r spanning over 10 million base-pairs. Besides classical imprinted expression that shows near exclusive maternal or paternal expression, widespread biased imprinted expression has been identified mainly in brain. In this review we discuss recent developments mapping cell type specific imprinted expression in extra-embryonic tissues and neocortex in the mouse. We highlight the advantages of using an inducible uniparental chromosome disomy (UPD) system to generate cells carrying either two maternal or two paternal copies of a specific chromosome to analyze the functional consequences of genomic imprinting. Mosaic Analysis with Double Markers (MADM) allows fluorescent labeling and concomitant induction of UPD sparsely in specific cell types, and thus to over-express or suppress all imprinted genes on that chromosome. To illustrate the utility of this technique, we explain how MADM-induced UPD revealed new insights about the function of the well-studied Cdkn1c imprinted gene, and how MADM-induced UPDs led to identification of highly cell type specific phenotypes related to perturbed imprinted expression in the mouse neocortex. Finally, we give an outlook on how MADM could be used to probe cell type specific imprinted expression in other tissues in mouse, particularly in extra-embryonic tissues.]]> Wed, 31 Dec 1969 19:00:00 EST Zebrafish as the toxicant screening model: Transgenic and omics approaches. Lai KP, Gong Z, Tse WKF
Aquat Toxicol (Mar 2021)

The production of large amounts of synthetic industrial and biomedical compounds, together with environmental pollutants, poses a risk to our ecosystem and induces negative effects on the health of wildlife and human beings. With the emergence of the global problem of chemical contamination, the adverse biological effects of these chemicals are gaining attention among the scientific communities, industry, governments, and the public. Among these chemicals, endocrine disrupting chemicals (EDCs) are regarded as one of the major global issues that potentially affecting our health. There is an urgent need of understanding the potential hazards of such chemicals. Zebrafish have been widely used in the aquatic toxicology. In this review, we first discuss the strategy of transgenic lines that used in the toxicological studies, followed by summarizing the current omics approaches (transcriptomics, proteomics, metabolomics, and epigenomics) on toxicities of EDCs in this model. We will also discuss the possible transgenerational effects in zebrafish and future prospective of the integrated omics approaches with customized transgenic organism. To conclude, we summarize the current findings in the field, and provide our opinions on future environmental toxicity research in the zebrafish model.]]> Wed, 31 Dec 1969 19:00:00 EST Integrative analysis of epigenomics, transcriptomics, and proteomics to identify key targets and pathways of Weining granule for gastric cancer. Liang MK, Liang XQ, Zhong J, Wei YT, Lian ZP, Huang ZK, Liang J
J Ethnopharmacol (Apr 2021)

Weining granule (WNG) is a "Qi-Enriching and Kidney-Tonifying, Spleen-Reinforcing and Stasis-Removing" formula for gastric cancer (GC). Past research we noted WNG inhibited cell growth and raised apoptosis in GC. However, the underlying mechanism of WNG for GC have yet to be systematically clarified.]]> Wed, 31 Dec 1969 19:00:00 EST Genomics and epigenomics of addiction. Maldonado R, Calvé P, García-Blanco A, Domingo-Rodriguez L, Senabre E, Martín-García E
Am J Med Genet B Neuropsychiatr Genet (Apr 2021)

Recent progress in the genomics and epigenomics of addiction has contributed to improving our understanding of this complex mental disorder's etiology, filling the gap between genes, environment, and behavior. We review the behavioral genetic studies reporting gene and environment interactions that explain the polygenetic contribution to the resilience and vulnerability to develop addiction. We discuss the evidence of polymorphic candidate genes that confer susceptibility to develop addiction as well as the studies of specific epigenetic marks that contribute to vulnerability and resilience to addictive-like behavior. A particular emphasis has been devoted to the miRNA changes that are considered potential biomarkers. The increasing knowledge about the technology required to alter miRNA expression may provide promising novel therapeutic tools. Finally, we give future directions for the field's progress in disentangling the connection between genes, environment, and behavior.]]> Wed, 31 Dec 1969 19:00:00 EST DNA methylome, transcriptome, and prostate cancer prevention by phenethyl isothiocyanate in TRAMP mice. Wu R, Li S, Sargsyan D, Yin R, Kuo HC, Peter R, Wang L, Hudlikar R, Liu X, Kong AN
Mol Carcinog (Apr 2021)

Epigenetics/epigenomics has been shown to be involved in carcinogenesis. However, how the epigenome would be altered in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and the effect of cancer chemopreventive phytochemical phenethyl isothiocyanate (PEITC) on the epigenome in TRAMP mice are not known. PEITC has been reported to reduce the risk of many cancers including prostate cancer (PCa). In this study, male TRAMP mice were fed a control diet or diet containing 0.05% PEITC from 8 weeks to 16 weeks. The tumor incidence was reduced in the PEITC diet (0/6) as compared with the control diet (6/7). RNA-sequencing (RNA-seq) analyses on nontumor and tumor prostatic tissues revealed several pathways like cell cycle/Cdc42 signaling, inflammation, and cancer-related signaling, were activated in prostate tissues of TRAMP mice but were reversed or attenuated in TRAMP mice fed with PEITC diet. DNA CpG methyl-seq analyses showed that global methylation patterns of prostate samples from TRAMP mice were hugely different from those of wild-type mice. Dietary PEITC partially reversed the global methylation changes during prostatic carcinogenesis. Integration of RNA-seq and DNA methyl-seq analyses identified a list of genes, including Adgrb1 and Ebf4, with an inverse regulatory relationship between their RNA expression and CpG methylation. In summary, our current study demonstrates that alteration of the global epigenome in TRAMP prostate tumor and PEITC administration suppresses PCa carcinogenesis, impacts global CpG epigenome and transcriptome, and attenuates carcinogenic pathways like cell cycle arrest and inflammation. These results may provide insights and epigenetic markers/targets for PCa prevention and treatment in human PCa patients.]]> Wed, 31 Dec 1969 19:00:00 EST DeFusion: a denoised network regularization framework for multi-omics integration. Wang W, Zhang X, Dai DQ
Brief Bioinform (Apr 2021)

With diverse types of omics data widely available, many computational methods have been recently developed to integrate these heterogeneous data, providing a comprehensive understanding of diseases and biological mechanisms. But most of them hardly take noise effects into account. Data-specific patterns unique to data types also make it challenging to uncover the consistent patterns and learn a compact representation of multi-omics data. Here we present a multi-omics integration method considering these issues. We explicitly model the error term in data reconstruction and simultaneously consider noise effects and data-specific patterns. We utilize a denoised network regularization in which we build a fused network using a denoising procedure to suppress noise effects and data-specific patterns. The error term collaborates with the denoised network regularization to capture data-specific patterns. We solve the optimization problem via an inexact alternating minimization algorithm. A comparative simulation study shows the method's superiority at discovering common patterns among data types at three noise levels. Transcriptomics-and-epigenomics integration, in seven cancer cohorts from The Cancer Genome Atlas, demonstrates that the learned integrative representation extracted in an unsupervised manner can depict survival information. Specially in liver hepatocellular carcinoma, the learned integrative representation attains average Harrell's C-index of 0.78 in 10 times 3-fold cross-validation for survival prediction, which far exceeds competing methods, and we discover an aggressive subtype in liver hepatocellular carcinoma with this latent representation, which is validated by an external dataset GSE14520. We also show that DeFusion is applicable to the integration of other omics types.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic nucleotides enhance therapy. Kriaucionis S
Science (04 2021)

]]> Wed, 31 Dec 1969 19:00:00 EST An update on the management of chronic pelvic pain in women. Vincent K, Evans E
Anaesthesia (Apr 2021)

Chronic pelvic pain represents a major public health problem for women and impacts significantly on their quality of life. Yet it is under-researched and a challenge to manage. Women who suffer from chronic pelvic pain frequently describe their healthcare journey as long, via a variety of specialists and frustrating, with their pain often dismissed. Aetiological factors and associations are best conceptualised using the 'three P's' model of predisposing, precipitating and perpetuating factors. This integrates the numerous biological, psychological and social contributors to the complex, multifactorial nature of chronic pelvic pain. Overall management involves analgesia, hormonal therapies, physiotherapy, psychological approaches and lifestyle advice, which like other chronic pain conditions relies on a multidisciplinary team approach delivered by professionals experienced and trained in managing chronic pelvic pain.]]> Wed, 31 Dec 1969 19:00:00 EST Induced pluripotent stem cell technology: trends in molecular biology, from genetics to epigenetics. Maali A, Maroufi F, Sadeghi F, Atashi A, Kouchaki R, Moghadami M, Azad M
Epigenomics (Apr 2021)

Induced pluripotent stem cell (iPSC) technology, based on autologous cells' reprogramming to the embryonic state, is a new approach in regenerative medicine. Current advances in iPSC technology have opened up new avenues for multiple applications, from basic research to clinical therapy. Thus, conducting iPSC trials have attracted increasing attention and requires an extensive understanding of the molecular basis of iPSCs. Since iPSC reprogramming is based on the methods inducing the expression of specific genes involved in pluripotency states, it can be concluded that iPSC reprogramming is strongly influenced by epigenetics. In this study, we reviewed the molecular basis of reprogramming, including the reprogramming factors (OCT4, SOX2, KLF4, c-MYC, NANOG, ESRRB, LIN28 as well as their regulatory networks), applied vectors (retroviral vectors, adenoviral vectors, Sendaiviral vectors, episomal plasmids, piggyBac, simple vectors, etc.) and epigenetic modifications (miRNAs, histones and DNA methylation states) to provide a comprehensive guide for reprogramming studies.]]> Wed, 31 Dec 1969 19:00:00 EST Changes of DNA Methylation Patterns Reveal Epigenetic Modification of Dormancy Release-Related Genes Is Induced by Chilling in Tree Peony. Zhang Y, Zhang T, Si F, Wang X, Liu C, Yuan Y, Feng W, Gai S
DNA Cell Biol (Apr 2021)

DNA methylation is an important epigenetic regulator of gene expression. Application of 5-azacytidine (a methylation inhibitor) significantly promoted bud sprouting rate and the elongation of branches and leaves in "Luhehong" and "Fengdanbai." In total, 11,166 and 11,443 fragments were obtained by methylation-sensitive amplified polymorphism (MSAP) analysis during chilling-induced dormancy release in the two varieties, respectively. Total methylation levels were high in dormant buds, mainly for hemimethylation, which were slowly increased by short-term chilling (7 days) and decreased by long-term chilling. Compared with 0 day, the ratio of the methylation downregulated group increased during dormancy release, whereas that of the upregulated group declined gradually. These variations were consistent with the dynamic expressions of DNA methyltransferase/demethylase genes and their enzyme activity changes. In total, 13 polymorphic MSAP fragments were similar to known proteins (-value <1e-5), and their methylation statuses were consistent with their expression patterns. The expression change of , encoding cell wall hydrolase, might be due to DNA methylation ratios of CpG sites identified by bisulfite sequencing. These results indicated that chilling accumulation promoted bud dormancy release and sprouting through DNA methylation modification of specific genes. This study would provide new insights into the molecular mechanism underlying dormancy release in tree peony.]]> Wed, 31 Dec 1969 19:00:00 EST