'; ?> 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, 09 Apr 2020 14:27:23 EDT Thu, 09 Apr 2020 14:27:23 EDT jirtle@radonc.duke.edu james001@jirtle.com Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity. Cheung K, Barter MJ, Falk J, Proctor CJ, Reynard LN, Young DA
FASEB J (Apr 2020)

Epigenetic mechanisms are known to regulate gene expression during chondrogenesis. In this study, we have characterized the epigenome during the in vitro differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes. Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) was used to assess a range of N-terminal posttranscriptional modifications (marks) to histone H3 lysines (H3K4me3, H3K4me1, H3K27ac, H3K27me3, and H3K36me3) in both hMSCs and differentiated chondrocytes. Chromatin states were characterized using histone ChIP-seq and cis-regulatory elements were identified in chondrocytes. Chondrocyte enhancers were associated with chondrogenesis-related gene ontology (GO) terms. In silico analysis and integration of DNA methylation data with chondrogenesis chromatin states revealed that enhancers marked by histone marks H3K4me1 and H3K27ac were de-methylated during in vitro chondrogenesis. Similarity analysis between hMSC and chondrocyte chromatin states defined in this study with epigenomes of cell-types defined by the Roadmap Epigenomics project revealed that enhancers are more distinct between cell-types compared to other chromatin states. Motif analysis revealed that the transcription factor SOX9 is enriched in chondrocyte enhancers. Luciferase reporter assays confirmed that chondrocyte enhancers characterized in this study exhibited enhancer activity which may be modulated by DNA methylation and SOX9 overexpression. Altogether, these integrated data illustrate the cross-talk between different epigenetic mechanisms during chondrocyte differentiation.]]>
Wed, 31 Dec 1969 19:00:00 EST
Imprinted Small RNAs Unraveled: Maternal MicroRNAs Antagonize a Paternal-Genome-Driven Gene Expression Network. Ghousein A, Feil R
Mol Cell (Apr 2020)

Whipple et al., 2020 describe that, in neurons, a dense cluster of maternally expressed microRNAs post-transcriptionally downregulates several imprinted genes expressed from the paternal genome-an antagonistic mechanism that modulates neuronal functions and provides insights into the evolution of genomic imprinting.]]>
Wed, 31 Dec 1969 19:00:00 EST
Multi-omics analysis at epigenomics and transcriptomics levels reveals prognostic subtypes of lung squamous cell carcinoma. Xu Y, She Y, Li Y, Li H, Jia Z, Jiang G, Liang L, Duan L
Biomed Pharmacother (May 2020)

In this study, we identified prognostic biomarkers for lung squamous cell carcinoma (LUSC) by integrating multiple sets of DNA copy number variants (CNV) and methylation variant (MET) data, and performing qPCR and immunohistochemical identification. We examined the expression of CNV and MET in 368 LUSC patients. Gene expression associated with DNA copy number or DNA methylation was identified and four LUSC gene subtypes were defined based on these correlations. The prognosis overall survival (OS) of the iC1 subtype was significantly lower than that in the iC2 and iC4 subtypes. We assessed the immune scores of each subtype and found that the six immune cell scores of the iC3 subtype were significantly higher than the other subtypes (p < 0.01). Three genes associated with prognosis, NFE2L2, ASAH2, and RIMBP2, were identified by comparing the expression of CNV and MET in subtypes. Analysis of mutational differences between subtypes revealed a group of genes with significant mutations between the iC1 and iC4 subtypes. The number of mutations in the NFE2L2 gene in LUSC was significantly higher than that in other genes, and the gene was prognostic. The number of mutations was significantly higher in the best iC4 subtype than the iC1 subtype with the worst prognosis; the other two genes, ASAH2 and RIMBP2, were only found in the worst prognosis of the iC1 subtype. This comprehensive multi-omics analysis of genomics, epigenomics, and transcriptomics data provides new insights into the molecular mechanisms of LUSC and may be helpful in identifying biomolecular markers for early disease diagnosis.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genomic Characterization of Endothelial Enhancers Reveals a Multifunctional Role for NR2F2 in Regulation of Arteriovenous Gene Expression. Sissaoui S, Yu J, Yan A, Li R, Yukselen O, Kucukural A, Zhu LJ, Lawson ND
Circ Res (Mar 2020)

Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Therefore, such studies are warranted to address this gap.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenomics and the kidney. Wilson PC, Ledru N, Humphreys BD
Curr Opin Nephrol Hypertens (May 2020)

Epigenetic modifications are reversible changes to a cell's DNA or histones that alter gene expression but not DNA sequence. The present review will explore epigenomic profiling and bioinformatics techniques for the study of kidney development and disease.]]>
Wed, 31 Dec 1969 19:00:00 EST
Multiview learning for understanding functional multiomics. Nguyen ND, Wang D
PLoS Comput Biol (Apr 2020)

The molecular mechanisms and functions in complex biological systems currently remain elusive. Recent high-throughput techniques, such as next-generation sequencing, have generated a wide variety of multiomics datasets that enable the identification of biological functions and mechanisms via multiple facets. However, integrating these large-scale multiomics data and discovering functional insights are, nevertheless, challenging tasks. To address these challenges, machine learning has been broadly applied to analyze multiomics. This review introduces multiview learning-an emerging machine learning field-and envisions its potentially powerful applications to multiomics. In particular, multiview learning is more effective than previous integrative methods for learning data's heterogeneity and revealing cross-talk patterns. Although it has been applied to various contexts, such as computer vision and speech recognition, multiview learning has not yet been widely applied to biological data-specifically, multiomics data. Therefore, this paper firstly reviews recent multiview learning methods and unifies them in a framework called multiview empirical risk minimization (MV-ERM). We further discuss the potential applications of each method to multiomics, including genomics, transcriptomics, and epigenomics, in an aim to discover the functional and mechanistic interpretations across omics. Secondly, we explore possible applications to different biological systems, including human diseases (e.g., brain disorders and cancers), plants, and single-cell analysis, and discuss both the benefits and caveats of using multiview learning to discover the molecular mechanisms and functions of these systems.]]>
Wed, 31 Dec 1969 19:00:00 EST
Plant stress biology in epigenomic era. Perrone A, Martinelli F
Plant Sci (May 2020)

Recent progress in "omics" methodologies allow us to gain insight into the complex molecular regulatory networks underlying plant responses to environmental stresses. Among the different genome-wide analysis, epigenomics is the most under-investigated "omic" approach requiring more critical and speculative discussion about approaches, methods and experimental designs. Epigenomics allows us to gain insight into the molecular adaptation of plants in response to environmental stresses. The identification of epigenetic marks transmitted during filial generations enables new theories to be developed on the evolution of living organisms in relation to environmental changes. The molecular mechanisms driving the capacity of plants to memorize a stress and to generate stress-resistant progenies are still unclear and scarcely investigated. The elucidation of these cryptic molecular switches will assist breeders in designing crops characterized by minimally compromised productivity in relation to stresses caused by climate change. The aim of this review is to briefly describe the most uptodate epigenomic approaches, update recent progresses in crop epigenomics in plant stress biology, and to stimulate the discussion of new epigenomic methods and approaches in the new era of "omic" sciences.]]>
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 (Apr 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
Epigenomics in acute cerebrovascular diseases. Tuttolomondo A, Pinto A
Epigenomics (Apr 2020)

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 (Jul 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
Molecular Mechanisms of Facultative Heterochromatin Formation: An X-Chromosome Perspective. Å»ylicz JJ, Heard E
Annu Rev Biochem (Apr 2020)

Facultative heterochromatin (fHC) concerns the developmentally regulated heterochromatinization of different regions of the genome and in the case of the mammalian X chromosome and imprinted loci, of only one allele of a homologous pair. The formation of fHC participates in the timely repression of genes, by resisting strong activators. In this review, we discuss the molecular mechanisms underlying the establishment and maintenance of fHC in mammals using a mouse model. We focus on X-chromosome inactivation (XCI) as a paradigm for fHC but also relate it to genomic imprinting and homeobox () gene cluster repression. A vital role for noncoding transcription and/or transcripts emerges as the general principle of triggering XCI and canonical imprinting. However, other types of fHC are established through an unknown mechanism, independent of noncoding transcription ( clusters and noncanonical imprinting). We also extensively discuss polycomb-group repressive complexes (PRCs), which frequently play a vital role in fHC maintenance. Expected final online publication date for the , Volume 89 is June 22, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.]]>
Wed, 31 Dec 1969 19:00:00 EST
Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons. Whipple AJ, Breton-Provencher V, Jacobs HN, Chitta UK, Sur M, Sharp PA
Mol Cell (Apr 2020)

Imprinted genes with parental-biased allelic expression are frequently co-regulated and enriched in common biological pathways. Here, we functionally characterize a large cluster of microRNAs (miRNAs) expressed from the maternally inherited allele ("maternally expressed") to explore the molecular and cellular consequences of imprinted miRNA activity. Using an induced neuron (iN) culture system, we show that maternally expressed miRNAs from the miR-379/410 cluster direct the RNA-induced silencing complex (RISC) to transcriptional and developmental regulators, including paternally expressed transcripts like Plagl1. Maternal deletion of this imprinted miRNA cluster resulted in increased protein levels of several targets and upregulation of a broader transcriptional program regulating synaptic transmission and neuronal function. A subset of the transcriptional changes resulting from miR-379/410 deletion can be attributed to de-repression of Plagl1. These data suggest maternally expressed miRNAs antagonize paternally driven gene programs in neurons.]]>
Wed, 31 Dec 1969 19:00:00 EST
Histone acetylation together with DNA demethylation empowers higher plasticity in adipocytes to differentiate into osteoblasts. Cho YD, Kim BS, Kim WJ, Kim HJ, Baek JH, Woo KM, Seol YJ, Ku Y, Ryoo HM
Gene (Apr 2020)

Bone regeneration has been a challenge for both researchers and clinicians. In the field of tissue engineering, much effort has been made to identify cell sources including stem cells. The present study aimed to induce trans-differentiation from adipocytes to osteoblasts using epigenetic modifiers; 5-aza-dC and/or trichostatin-A (TSA). 3 T3-L1 preadipocytes were treated with TSA (100 nM) and then with Wnt3a (50 ng/ml). Microscopic observation showed trans-differentiated cell morphology. Methylation-specific PCR and immunoblotting were performed to analyze the DNA methylation and histone acetylation patterns. The gene expression was determined by real-time PCR. Based on these in vitro experiments, in vivo mouse experiments supplemented the possibility of trans-differentiation by epigenetic modification. TSA induced the acetylation of lysine9 on histone H3, and a sequential Wnt3a treatment stimulated the expression of bone marker genes in adipocytes, suppressing adipogenesis and stimulating osteogenesis. Furthermore, TSA induced DNA hypomethylation, and a combined treatment with TSA and 5-aza-dC showed a synergistic effect in epigenetic modifications. The number of adipocytes and DNA methylation patterns of old (15 months) and young (6 weeks) mice were significantly different, and TSA and sequential Wnt3a treatments increased bone formation in the old mice. Collectively, our results confirmed cell trans-differentiation via epigenetic modifications and osteogenic signaling from adipocytes to osteoblasts for the bone regeneration in vitro and in vivo, and indicated that histone acetylation could induce DNA hypomethylation, enhancing the chance of trans-differentiation.]]>
Wed, 31 Dec 1969 19:00:00 EST
Childhood asthma in the new omics era: challenges and perspectives. Golebski K, Kabesch M, Melén E, Potočnik U, van Drunen CM, Reinarts S, Maitland-van der Zee AH, Vijverberg SJH,  
Curr Opin Allergy Clin Immunol (Apr 2020)

Childhood asthma is a heterogeneous inflammatory disease comprising different phenotypes and endotypes and, particularly in its severe forms, has a large impact on the quality-of-life of patients and caregivers. The application of advanced omics technologies provides useful insights into underlying asthma endotypes and may provide potential clinical biomarkers to guide treatment and move towards a precision medicine approach.]]>
Wed, 31 Dec 1969 19:00:00 EST
Cell Type-Specific Intralocus Interactions Reveal Oligodendrocyte Mechanisms in MS. Factor DC, Barbeau AM, Allan KC, Hu LR, Madhavan M, Hoang AT, Hazel KEA, Hall PA, Nisraiyya S, Najm FJ, Miller TE, Nevin ZS, Karl RT, Lima BR, Song Y, Sibert AG, Dhillon GK, Volsko C, Bartels CF, Adams DJ, Dutta R, Gallagher MD, Phu W, Kozlenkov A, Dracheva S, Scacheri PC, Tesar PJ, Corradin O
Cell (Apr 2020)

Multiple sclerosis (MS) is an autoimmune disease characterized by attack on oligodendrocytes within the central nervous system (CNS). Despite widespread use of immunomodulatory therapies, patients may still face progressive disability because of failure of myelin regeneration and loss of neurons, suggesting additional cellular pathologies. Here, we describe a general approach for identifying specific cell types in which a disease allele exerts a pathogenic effect. Applying this approach to MS risk loci, we pinpoint likely pathogenic cell types for 70%. In addition to T cell loci, we unexpectedly identified myeloid- and CNS-specific risk loci, including two sites that dysregulate transcriptional pause release in oligodendrocytes. Functional studies demonstrated inhibition of transcriptional elongation is a dominant pathway blocking oligodendrocyte maturation. Furthermore, pause release factors are frequently dysregulated in MS brain tissue. These data implicate cell-intrinsic aberrations outside of the immune system and suggest new avenues for therapeutic development. VIDEO ABSTRACT.]]>
Wed, 31 Dec 1969 19:00:00 EST
High polygenic burden is associated with blood DNA methylation changes in individuals with suicidal behavior. Cabrera-Mendoza B, Martínez-Magaña JJ, Genis-Mendoza AD, Sarmiento E, Ruíz-Ramos D, Tovilla-Zárate CA, González-Castro TB, Juárez-Rojop IE, García-de la Cruz DD, López-Armenta M, Real F, García-Dolores F, Flores G, Vázquez-Roque RA, Lanzagorta N, Escamilla M, Saucedo-Uribe E, Rodríguez-Mayoral O, Jiménez-Genchi J, Castañeda-González C, Roche-Bergua A, Nicolini H
J Psychiatr Res (Apr 2020)

Suicidal behavior is result of the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide). Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. We identified 153 differentially methylated sites between individuals with low and high-PRS. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment (CHD7, RFX4, KCNA1, PLCB1, PITX1, NUMBL) and ATP binding (KIF7, NUBP2, KIF6, ATP8B1, ATP11A, CLCN7, MYLK, MAP2K5). Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.]]>
Wed, 31 Dec 1969 19:00:00 EST
Co-localization between Sequence Constraint and Epigenomic Information Improves Interpretation of Whole-Genome Sequencing Data. Xu D, Wang C, Kiryluk K, Buxbaum JD, Ionita-Laza I
Am J Hum Genet (Apr 2020)

The identification of functional regions in the noncoding human genome is difficult but critical in order to gain understanding of the role noncoding variation plays in gene regulation in human health and disease. We describe here a co-localization approach that aims to identify constrained sequences that co-localize with tissue- or cell-type-specific regulatory regions, and we show that the resulting score is particularly well suited for the identification of rare regulatory variants. For 127 tissues and cell types in the ENCODE/Roadmap Epigenomics Project, we provide catalogs of putative tissue- or cell-type-specific regulatory regions under sequence constraint. We use the newly developed co-localization score for brain tissues to score de novo mutations in whole genomes from 1,902 individuals affected with autism spectrum disorder (ASD) and their unaffected siblings in the Simons Simplex Collection. We show that noncoding de novo mutations near genes co-expressed in midfetal brain with high confidence ASD risk genes, and near FMRP gene targets are more likely to be in co-localized regions if they occur in ASD probands versus in their unaffected siblings. We also observed a similar enrichment for mutations near lincRNAs, previously shown to co-express with ASD risk genes. Additionally, we provide strong evidence that prioritized de novo mutations in autism probands point to a small set of well-known ASD genes, the disruption of which produces relevant mouse phenotypes such as abnormal social investigation and abnormal discrimination/associative learning, unlike the de novo mutations in unaffected siblings. The genome-wide co-localization results are available online.]]>
Wed, 31 Dec 1969 19:00:00 EST
Single-Cell Multi-omics and Its Prospective Application in Cancer Biology. Peng A, Mao X, Zhong J, Fan S, Hu Y
Proteomics (Mar 2020)

Recent years, the emergence of single-cell omics technologies, which can profile genomics, transcriptomics, epigenomics, and proteomics, has provided unprecedented insights into characteristics of cancer, enabling higher resolution and accuracy to decipher the cellular and molecular mechanisms relating to tumorigenesis, evolution, metastasis, and immune responses. Single-cell multi-omics technologies, which were developed based on the combination of multiple single-cell mono-omics technologies, could simultaneously analyze RNA expression, single nucleotide polymorphism, epigenetic modification, or protein abundance, enabling the in-depth understanding of gene expression regulatory mechanisms. In this review, we summarize the state-of-the-art single-cell multi-omics technologies and discuss the prospects of their application in cancer biology. This article is protected by copyright. All rights reserved.]]>
Wed, 31 Dec 1969 19:00:00 EST
TADsplimer reveals splits and mergers of topologically associating domains for epigenetic regulation of transcription. Wang G, Meng Q, Xia B, Zhang S, Lv J, Zhao D, Li Y, Wang X, Zhang L, Cooke JP, Cao Q, Chen K
Genome Biol (Apr 2020)

We present TADsplimer, the first computational tool to systematically detect topologically associating domain (TAD) splits and mergers across the genome between Hi-C samples. TADsplimer recaptures splits and mergers of TADs with high accuracy in simulation analyses and defines hundreds of TAD splits and mergers between pairs of different cell types, such as endothelial cells and fibroblasts. Our work reveals a key role for TAD remodeling in epigenetic regulation of transcription and delivers the first tool for the community to perform dynamic analysis of TAD splits and mergers in numerous biological and disease models.]]>
Wed, 31 Dec 1969 19:00:00 EST
Paternally-biased gene expression follows kin-selected predictions in female honey bee embryos. Smith NMA, Yagound B, Remnant EJ, Foster CSP, Buchmann G, Allsopp MH, Kent CF, Zayed A, Rose SA, Lo K, Ashe A, Harpur BA, Beekman M, Oldroyd BP
Mol Ecol (Mar 2020)

The Kinship Theory of Genomic Imprinting (KTGI) posits that, in species where females mate with multiple males, there is selection for a male to enhance the reproductive success of his offspring at the expense of other males and his mating partner. Reciprocal crosses between honey bee subspecies show parent-of-origin effects for reproductive traits, suggesting that males modify the expression of genes related to female function in their female offspring. This effect is likely to be greater in the Cape honey bee (Apis mellifera capensis), because a male's daughters have the unique ability to produce female offspring that can develop into reproductive workers or the next queen without mating. We generated reciprocal crosses between Capensis and another subspecies and used RNA-seq to identify transcripts that are over- or under-expressed in the embryos, depending on the parental origin of the gene. As predicted, 21 genes showed expression bias towards the Capensis father's allele in colonies with a Capensis father, with no such bias in the reciprocal cross. A further six genes showed a consistent bias towards expression of the father's allele across all eight colonies examined, regardless of the direction of the cross. Consistent with predictions of the KTGI, six of the 21 genes are associated with female reproduction. No gene consistently showed over-expression of the maternal allele.]]>
Wed, 31 Dec 1969 19:00:00 EST