'; ?> 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, 25 Jan 2020 03:48:31 EST Sat, 25 Jan 2020 03:48:31 EST jirtle@radonc.duke.edu james001@jirtle.com Placental effects on the maternal brain revealed by disrupted placental gene expression in mouse hybrids. Arévalo L, Campbell P
Proc Biol Sci (Jan 2020)

The mammalian placenta is both the physical interface between mother and fetus, and the source of endocrine signals that target the maternal hypothalamus, priming females for parturition, lactation and motherhood. Despite the importance of this connection, the effects of altered placental signalling on the maternal brain are insufficiently studied. Here, we show that placental dysfunction alters gene expression in the maternal brain, with the potential to affect maternal behaviour. Using a cross between the house mouse and the Algerian mouse, in which hybrid placental development is abnormal, we sequenced late-gestation placental and maternal medial preoptic area transcriptomes and quantified differential expression and placenta-maternal brain co-expression between normal and hybrid pregnancies. The expression of and was significantly altered in the brains of females exposed to hybrid placentas. Most strikingly, expression patterns of placenta-specific gene families and in the brains of house mouse females carrying hybrid litters matched those of female Algerian mice, the paternal species in the cross. Our results indicate that the paternally derived placental genome can influence the expression of maternal-fetal communication genes, including placental hormones, suggesting an effect of the offspring's father on the mother's brain.]]>
Wed, 31 Dec 1969 19:00:00 EST
Editing DNA Methylation in Mammalian Embryos. Yamazaki T, Hatano Y, Taniguchi R, Kobayashi N, Yamagata K
Int J Mol Sci (Jan 2020)

DNA methylation in mammals is essential for numerous biological functions, such as ensuring chromosomal stability, genomic imprinting, and X-chromosome inactivation through transcriptional regulation. Gene knockout of DNA methyltransferases and demethylation enzymes has made significant contributions to analyzing the functions of DNA methylation in development. By applying epigenome editing, it is now possible to manipulate DNA methylation in specific genomic regions and to understand the functions of these modifications. In this review, we first describe recent DNA methylation editing technology. We then focused on changes in DNA methylation status during mammalian gametogenesis and preimplantation development, and have discussed the implications of applying this technology to early embryos.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetics/epigenomics and prevention by curcumin of early stages of inflammatory-driven colon cancer. Wu R, Wang L, Yin R, Hudlikar R, Li S, Kuo HD, Peter R, Sargsyan D, Guo Y, Liu X, Kong AT
Mol Carcinog (Feb 2020)

Colorectal cancer (CRC) is associated with significant morbidity and mortality in the US and worldwide. CRC is the second most common cancer-related death in both men and women globally. Chronic inflammation has been identified as one of the major risk factors of CRC. It may drive genetic and epigenetic/epigenomic alterations, such as DNA methylation, histone modification, and non-coding RNA regulation. Current prevention modalities for CRC are limited and some treatment regimens such as use the nonsteroidal anti-inflammatory drug aspirin may have severe side effects, namely gastrointestinal ulceration and bleeding. Therefore, there is an urgent need of developing alternative strategies. Recently, increasing evidence suggests that several dietary cancer chemopreventive phytochemicals possess anti-inflammation and antioxidative stress activities, and may prevent cancers including CRC. Curcumin (CUR) is the yellow pigment that is found in the rhizomes of turmeric (Curcuma longa). Many studies have demonstrated that CUR exhibit strong anticancer, antioxidative stress, and anti-inflammatory activities by regulating signaling pathways, such as nuclear factor erythroid-2-related factor 2, nuclear factor-κB, and epigenetics/epigenomics pathways of histones modifications, and DNA methylation. In this review, we will discuss the latest evidence in epigenetics/epigenomics alterations by CUR in CRC and their potential contribution in the prevention of CRC.]]>
Wed, 31 Dec 1969 19:00:00 EST
Using What We Already Have: Uncovering New Drug Repurposing Strategies in Existing Omics Data. Pulley JM, Rhoads JP, Jerome RN, Challa AP, Erreger KB, Joly MM, Lavieri RR, Perry KE, Zaleski NM, Shirey-Rice JK, Aronoff DM
Annu Rev Pharmacol Toxicol (Jan 2020)

The promise of drug repurposing is to accelerate the translation of knowledge to treatment of human disease, bypassing common challenges associated with drug development to be more time- and cost-efficient. Repurposing has an increased chance of success due to the previous validation of drug safety and allows for the incorporation of omics. Hypothesis-generating omics processes inform drug repurposing decision-making methods on drug efficacy and toxicity. This review summarizes drug repurposing strategies and methodologies in the context of the following omics fields: genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, phenomics, pregomics, and personomics. While each omics field has specific strengths and limitations, incorporating omics into the drug repurposing landscape is integral to its success.]]>
Wed, 31 Dec 1969 19:00:00 EST
A road map for understanding molecular and genetic determinants of osteoporosis. Yang TL, Shen H, Liu A, Dong SS, Zhang L, Deng FY, Zhao Q, Deng HW
Nat Rev Endocrinol (Feb 2020)

Osteoporosis is a highly prevalent disorder characterized by low bone mineral density and an increased risk of fracture, termed osteoporotic fracture. Notably, bone mineral density, osteoporosis and osteoporotic fracture are highly heritable; however, determining the genetic architecture, and especially the underlying genomic and molecular mechanisms, of osteoporosis in vivo in humans is still challenging. In addition to susceptibility loci identified in genome-wide association studies, advances in various omics technologies, including genomics, transcriptomics, epigenomics, proteomics and metabolomics, have all been applied to dissect the pathogenesis of osteoporosis. However, each technology individually cannot capture the entire view of the disease pathology and thus fails to comprehensively identify the underlying pathological molecular mechanisms, especially the regulatory and signalling mechanisms. A change to the status quo calls for integrative multi-omics and inter-omics analyses with approaches in 'systems genetics and genomics'. In this Review, we highlight findings from genome-wide association studies and studies using various omics technologies individually to identify mechanisms of osteoporosis. Furthermore, we summarize current studies of data integration to understand, diagnose and inform the treatment of osteoporosis. The integration of multiple technologies will provide a road map to illuminate the complex pathogenesis of osteoporosis, especially from molecular functional aspects, in vivo in humans.]]>
Wed, 31 Dec 1969 19:00:00 EST
CHROMATIX: computing the functional landscape of many-body chromatin interactions in transcriptionally active loci from deconvolved single cells. Perez-Rathke A, Sun Q, Wang B, Boeva V, Shao Z, Liang J
Genome Biol (Jan 2020)

Chromatin interactions are important for gene regulation and cellular specialization. Emerging evidence suggests many-body spatial interactions play important roles in condensing super-enhancer regions into a cohesive transcriptional apparatus. Chromosome conformation studies using Hi-C are limited to pairwise, population-averaged interactions; therefore unsuitable for direct assessment of many-body interactions. We describe a computational model, CHROMATIX, which reconstructs ensembles of single-cell chromatin structures by deconvolving Hi-C data and identifies significant many-body interactions. For a diverse set of highly active transcriptional loci with at least 2 super-enhancers, we detail the many-body functional landscape and show DNase accessibility, POLR2A binding, and decreased H3K27me3 are predictive of interaction-enriched regions.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetic reprogramming in periodontal disease: Dynamic crosstalk with potential impact in oncogenesis. Barros SP, Fahimipour F, Tarran R, Kim S, Scarel-Caminaga RM, Justice A, North K
Periodontol 2000 (Feb 2020)

Periodontitis is a chronic multifactorial inflammatory disease associated with microbial dysbiosis and characterized by progressive destruction of the periodontal tissues. Such chronic infectious inflammatory disease is recognized as a major public health problem worldwide with measurable impact in systemic health. It has become evident that the periodontal disease phenotypes are not only determined by the microbiome effect, but the extent of the tissue response is also driven by the host genome and epigenome patterns responding to various environmental exposures. More recently there is mounting evidence indicating that epigenetic reprogramming in response to combined intrinsic and environmental exposures, might be particularly relevant due its plasticity and potential application towards precision health. The complex epigenetic crosstalk is reflected in the prognosis and progress of periodontal diseases and may also lead to a favorable landscape for cancer development. This review discusses epigenomics modifications focusing on the role of DNA methylation and pathways linking microbial infection and inflammatory pathways, which are also associated with carcinogenesis. There is a more clear vision whereas 'omics' technologies applied to unveil relevant epigenetic factors could play a significant role in the treatment of periodontal disease in a personalized mode, evidencing that public health approach should coexist with precision individualized treatment.]]>
Wed, 31 Dec 1969 19:00:00 EST
Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Laukoter S, Beattie R, Pauler FM, Amberg N, Nakayama KI, Hippenmeyer S
Nat Commun (Jan 2020)

The cyclin-dependent kinase inhibitor p57 is encoded by the imprinted Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex development. How Cdkn1c regulates corticogenesis is however not clear. To this end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous Cdkn1c function which at the mechanistic level mediates radial glial progenitor cell and nascent projection neuron survival. Strikingly, the growth-promoting function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting. Collectively, our results suggest that the Cdkn1c locus regulates cortical development through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally, our study highlights the importance to probe the relative contributions of cell intrinsic gene function and tissue-wide mechanisms to the overall phenotype.]]>
Wed, 31 Dec 1969 19:00:00 EST
ZNF597 is a maternally expressed imprinted gene in the Holstein breed. Gu S, Li J, Chen W, Li D, Zhang C, Li R, Xu D, Zhang C, Li S
Theriogenology (Feb 2020)

Genomic imprinting is an epigenetic phenomenon that leads to the preferential expression of genes from either the paternal or maternal allele. Imprinted genes play important roles in mammalian growth and development and a central role in placental function. ZNF597 and NAA60 are two paternally imprinted genes in the human ZNF597-NAA60 imprinted locus, both of which show biallelic expression in the mouse, but their imprinting status in cattle is still unknown. In this study, we examined the allelic expression of ZNF597 and NAA60 in adult bovine placental and somatic tissues. By comparing the mRNA-based genotypes with the genomic DNA-based genotypes, we identified monoallelic expression of ZNF597 in the placenta and in seven other tissues, including the cerebrum, heart, liver, spleen, lung, kidney, and muscle. Nevertheless, analysis revealed biallelic expression of the NAA60 gene in these tissues. Moreover, we tested the imprinting status of ZNF597 and confirmed that the maternal allele is expressed in the bovine placenta. To determine the role of DNA methylation in regulating monoallelic/imprinted expression of bovine ZNF597, the methylation status of two CpG-enriched regions in the bovine ZNF597-NAA60 locus was analyzed using the bisulfite sequencing method. Differentially methylated regions were detected on ten CpG loci in the bovine ZNF597 promoter region. In summary, the bovine ZNF597 gene is a maternally expressed gene, and its expression is regulated by DNA methylation, whereas the NAA60 gene is not imprinted in cattle.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetic Modifications in T Cells: The Role of DNA Methylation in Salt-Sensitive Hypertension. Dasinger JH, Alsheikh AJ, Abais-Battad JM, Pan X, Fehrenbach DJ, Lund H, Roberts ML, Cowley AW, Kidambi S, Kotchen TA, Liu P, Liang M, Mattson DL
Hypertension (Feb 2020)

The SS (Dahl salt sensitive) rat is an established model of hypertension and renal damage that is accompanied with immune system activation in response to a high-salt diet. Investigations into the effects of sodium-independent and dependent components of the diet were shown to affect the disease phenotype with SS/MCW (JrHsdMcwi) rats maintained on a purified diet (AIN-76A) presenting with a more severe phenotype relative to grain-fed SS/CRL (JrHsdMcwiCrl) rats. Since contributions of the immune system, environment, and diet are documented to alter this phenotype, this present study examined the epigenetic profile of T cells isolated from the periphery and the kidney from these colonies. T cells isolated from kidneys of the 2 colonies revealed that transcriptomic and functional differences may contribute to the susceptibility of hypertension and renal damage. In response to high-salt challenge, the methylome of T cells isolated from the kidney of SS/MCW exhibit a significant increase in differentially methylated regions with a preference for hypermethylation compared with the SS/CRL kidney T cells. Circulating T cells exhibited similar methylation profiles between colonies. Utilizing transcriptomic data from T cells isolated from the same animals upon which the DNA methylation analysis was performed, a predominant negative correlation was observed between gene expression and DNA methylation in all groups. Lastly, inhibition of DNA methyltransferases blunted salt-induced hypertension and renal damage in the SS/MCW rats providing a functional role for methylation. This study demonstrated the influence of epigenetic modifications to immune cell function, highlighting the need for further investigations.]]>
Wed, 31 Dec 1969 19:00:00 EST
Targeting epigenetic regulators in the treatment of T-cell lymphoma. Ahmed N, Feldman AL
Expert Rev Hematol (Jan 2020)

: T-cell lymphomas represent a broad group of malignant T-cell neoplasms with marked molecular, clinical, and biologic heterogeneity. Survival rates after conventional chemotherapy regimens are poor for most subtypes and new therapies are needed. Rapidly expanding knowledge in the field of epigenomics and the development of an increasing number of epigenetic-modifying agents have created new opportunities for epigenetic therapies for patients with this complex group of diseases.: The present review summarizes current knowledge on epigenetic alterations in T-cell lymphomas, availability, and mechanisms of action of epigenetic-modifying agents, results of clinical trials of epigenetic therapies in T-cell lymphomas, status of FDA approval, and biomarker approaches to guide therapy. Promising future directions are discussed.: Mutations in epigenetic-modifying genes are among the most common genetic alterations in T-cell lymphomas, highlighting the potential for epigenetic therapies to improve management of this group of diseases. Single-agent efficacy is well documented, leading to FDA approval for several indications, but overall response rates and durability of responses remain modest. Critical next steps for the field include optimizing combination therapies that incorporate epigenetic-modifying agents and developing predictive biomarkers that help guide patient and drug selection.]]>
Wed, 31 Dec 1969 19:00:00 EST
Museum Epigenomics: Charting the Future by Unlocking the Past. Hahn EE, Grealy A, Alexander M, Holleley CE
Trends Ecol Evol (Jan 2020)

Epigenomic state preserved in museum specimens could be leveraged to provide unique insights into gene regulation trends associated with accelerating environmental change during the Anthropocene. We address the challenges facing museum epigenomics and propose a collaborative framework for researchers and curators to explore this new field.]]>
Wed, 31 Dec 1969 19:00:00 EST
Transcriptional memory in skeletal muscle. Don't forget (to) exercise. Beiter T, Nieß AM, Moser D
J Cell Physiol (Jan 2020)

Transcriptional memory describes an ancient and highly conserved form of cellular learning that enables cells to benefit from recent experience by retaining a mitotically inheritable but reversible memory of the initial transcriptional response when encountering an environmental or physiological stimulus. Herein, we will review recent progress made in the understanding of how cells can make use of diverse constituents of the epigenetic toolbox to retain a transcriptional memory of past states and perturbations. Specifically, we will outline how these mechanisms will help to improve our understanding of skeletal muscle plasticity in health and disease. We describe the epigenetic road map that allows skeletal muscle fibers to navigate through training-induced adaptation processes, and how epigenetic memory marks can preserve an autobiographical history of lifestyle behavior changes, pathological challenges, and aging. We will further consider some key findings in the field of exercise epigenomics to emphasize major challenges when interpreting dynamic changes in the chromatin landscape in response to acute exercise and training.]]>
Wed, 31 Dec 1969 19:00:00 EST
Brain Development in School-Age and Adolescent Girls: Effects of Turner Syndrome, Estrogen Therapy, and Genomic Imprinting. O'Donoghue S, Green T, Ross JL, Hallmayer J, Lin X, Jo B, Huffman LC, Hong DS, Reiss AL
Biol Psychiatry (Jan 2020)

The study of Turner syndrome (TS) offers a unique window of opportunity for advancing scientific knowledge of how X chromosome gene imprinting, epigenetic factors, hormonal milieu, and chronologic age affect brain development in females.]]>
Wed, 31 Dec 1969 19:00:00 EST
A Multi-Omics Interpretable Machine Learning Model Reveals Modes of Action of Small Molecules. Patel-Murray NL, Adam M, Huynh N, Wassie BT, Milani P, Fraenkel E
Sci Rep (Jan 2020)

High-throughput screening and gene signature analyses frequently identify lead therapeutic compounds with unknown modes of action (MoAs), and the resulting uncertainties can lead to the failure of clinical trials. We developed an approach for uncovering MoAs through an interpretable machine learning model of transcriptomics, epigenomics, metabolomics, and proteomics. Examining compounds with beneficial effects in models of Huntington's Disease, we found common MoAs for compounds with unrelated structures, connectivity scores, and binding targets. The approach also predicted highly divergent MoAs for two FDA-approved antihistamines. We experimentally validated these effects, demonstrating that one antihistamine activates autophagy, while the other targets bioenergetics. The use of multiple omics was essential, as some MoAs were virtually undetectable in specific assays. Our approach does not require reference compounds or large databases of experimental data in related systems and thus can be applied to the study of agents with uncharacterized MoAs and to rare or understudied diseases.]]>
Wed, 31 Dec 1969 19:00:00 EST
Identification of a Novel Imprinted Transcript in the Porcine Complex Locus Using Methylome and Transcriptome of Parthenogenetic Fetuses. Ahn J, Wu H, Lee J, Hwang IS, Yu D, Ahn JS, Lee JW, Hwang S, Lee K
Genes (Basel) (Jan 2020)

Genomic imprinting in domestic animals contributes to the variance of performance traits. However, research remains to be done on large-scale detection of epigenetic landscape of porcine imprinted loci including the GNAS complex locus. The purpose of this study was to generate porcine parthenogenetic fetuses and comprehensively identify imprinting patterns of the GNAS locus in transcript levels. To this end, both normally fertilized and bimaternal (uniparental) parthenogenetic porcine fetuses were generated, and whole genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) were performed to construct methylome and transcriptome, respectively. Differentially methylated regions (DMRs) between the fetuses were identified through methylome analysis, and parental-origin-specific expression patterns of transcripts were examined with transcriptome. As a result, three major DMRs were identified: paternally methylated DMR, maternally methylated - DMR, and maternally methylated DMR. Parental-origin-specific expressions of those five DMR-affected transcripts were found, including a novel imprinted transcript, Exon1B, in pigs. In conclusion, using parthenotes, parental-origin-specific imprinting patterns in the porcine GNAS locus was comprehensively identified, and our approach paves the way for the discovery of novel imprinted genes and loci in a genomic context across species.]]>
Wed, 31 Dec 1969 19:00:00 EST
Identification of key genes by integrating DNA methylation and next-generation transcriptome sequencing for esophageal squamous cell carcinoma. Chen Y, Liao LD, Wu ZY, Yang Q, Guo JC, He JZ, Wang SH, Xu XE, Wu JY, Pan F, Lin DC, Xu LY, Li EM
Aging (Albany NY) (Jan 2020)

Aberrant DNA methylation leads to abnormal gene expression, making it a significant regulator in the progression of cancer and leading to the requirement for integration of gene expression with DNA methylation. Here, we identified 120 genes demonstrating an inverse correlation between DNA methylation and mRNA expression in esophageal squamous cell carcinoma (ESCC). Sixteen key genes, such as SIX4, CRABP2, and EHD3, were obtained by filtering 10 datasets and verified in paired ESCC samples by qRT-PCR. 5-Aza-dC as a DNA methyltransferase (DNMT) inhibitor could recover their expression and inhibit clonal growth of cancer cells in seven ESCC cell lines. Furthermore, 11 of the 16 genes were correlated with OS (overall survival) and DFS (disease-free survival) in 125 ESCC patients. ChIP-Seq data and WGBS data showed that DNA methylation and H3K27ac histone modification of these key genes displayed inverse trends, suggesting that there was collaboration between DNA methylation and histone modification in ESCC. Our findings illustrate that the integrated multi-omics data (transcriptome and epigenomics) can accurately obtain potential prognostic biomarkers, which may provide important insight for the effective treatment of cancers.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genome-wide analysis of epigenetic and transcriptional changes associated with heterosis in pigeonpea. Sinha P, Singh VK, Saxena RK, Kale SM, Li Y, Garg V, Tang M, Khan AW, Kim KD, Chitikineni A, Saxena KB, Sameer Kumar CV, Liu X, Xu X, Jackson S, Powell W, Nevo E, Searle IR, Lodha M, Varshney RK
Plant Biotechnol J (Jan 2020)

Hybrids are extensively used in agriculture to deliver an increase in yield, yet the molecular basis of heterosis is not well understood. Global DNA methylation analysis, transcriptome analysis and small RNA profiling were aimed to understand the epigenetic effect of the changes in gene expression level in the two hybrids and their parental lines. Increased DNA methylation was observed in both the hybrids as compared to their parents. This increase DNA methylation in hybrids showed that majority of the 24-nt sRNA clusters had higher expression in hybrids than the parents. Transcriptome analysis revealed that various phytohormones (auxin and salicylic acid) responsive hybrid-MPV DEGs were significantly altered in both the hybrids in comparison to MPV. DEGs associated with plant immunity and growth were overexpressed whereas DEGs associated with basal defense level were repressed. This antagonistic patterns of gene expression might contribute to the greater growth of the hybrids. It was also noticed that some common as well as unique changes in regulatory pathways associated with heterotic growth in both the hybrids. Approximately 70% and 67% of down-regulated hybrid-MPV DEGs were found to be differentially methylated in ICPH 2671 and ICPH 2740 hybrid, respectively. This reflected the association of epigenetic regulation in altered gene expressions. Our findings also revealed that miRNAs might play important roles in hybrid vigor in both the hybrids by regulating their target genes, especially in controlling plant growth and development, defense and stress response pathways. The above finding provides an insight into the molecular mechanism of pigeonpea heterosis.]]>
Wed, 31 Dec 1969 19:00:00 EST
Novel Approaches for Identifying the Molecular Background of Schizophrenia. Golov AK, Kondratyev NV, Kostyuk GP, Golimbet AVE
Cells (Jan 2020)

Recent advances in psychiatric genetics have led to the discovery of dozens of genomic loci associated with schizophrenia. However, a gap exists between the detection of genetic associations and understanding the underlying molecular mechanisms. This review describes the basic approaches used in the so-called post-GWAS studies to generate biological interpretation of the existing population genetic data, including both molecular (creation and analysis of knockout animals, exploration of the transcriptional effects of common variants in human brain cells) and computational (fine-mapping of causal variability, gene set enrichment analysis, partitioned heritability analysis) methods. The results of the crucial studies, in which these approaches were used to uncover the molecular and neurobiological basis of the disease, are also reported.]]>
Wed, 31 Dec 1969 19:00:00 EST
Understanding epigenomics based on the rice model. Lu Y, Zhou DX, Zhao Y
Theor Appl Genet (Jan 2020)

The purpose of this paper provides a comprehensive overview of the recent researches on rice epigenomics, including DNA methylation, histone modifications, noncoding RNAs, and three-dimensional genomics. The challenges and perspectives for future research in rice are discussed. Rice as a model plant for epigenomic studies has much progressed current understanding of epigenetics in plants. Recent results on rice epigenome profiling and three-dimensional chromatin structure studies reveal specific features and implication in gene regulation during rice plant development and adaptation to environmental changes. Results on rice chromatin regulator functions shed light on mechanisms of establishment, recognition, and resetting of epigenomic information in plants. Cloning of several rice epialleles associated with important agronomic traits highlights importance of epigenomic variation in rice plant growth, fitness, and yield. In this review, we summarize and analyze recent advances in rice epigenomics and discuss challenges and directions for future research in the field.]]>
Wed, 31 Dec 1969 19:00:00 EST