'; ?> 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, 26 Nov 2020 02:39:48 EST Thu, 26 Nov 2020 02:39:48 EST jirtle@radonc.duke.edu james001@jirtle.com Dysregulation of Transcription Factor Activity During Formation of Cancer-Associated Fibroblasts. Kapusta P, Dulińska-Litewka J, Totoń-Å»urańska J, Borys A, Konieczny PS, Wołkow PP, Seweryn MT
Int J Mol Sci (Nov 2020)

The reciprocal interactions between cancer cells and the quiescent fibroblasts leading to the activation of cancer-associated fibroblasts (CAFs) serve an important role in cancer progression. Here, we investigated the activation of transcription factors (TFs) in prostate fibroblasts (WPMY cell line) co-cultured with normal prostate or tumorous cells (RWPE1 and RWPE2 cell lines, respectively). After indirect co-cultures, we performed mRNA-seq and predicted TF activity using mRNA expression profiles with the Systems EPigenomics Inference of Regulatory Activity (SEPIRA) package and the GTEx and mRNA-seq data of 483 cultured fibroblasts. The initial differential expression analysis between time points and experimental conditions showed that co-culture with normal epithelial cells mainly promotes an inflammatory response in fibroblasts, whereas with the cancerous epithelial, it stimulates transformation by changing the expression of the genes associated with microfilaments. TF activity analysis revealed only one positively regulated TF in the RWPE1 co-culture alone, while we observed dysregulation of 45 TFs (7 decreased activity and 38 increased activity) uniquely in co-culture with RWPE2. Pathway analysis showed that these 45 dysregulated TFs in fibroblasts co-cultured with RWPE2 cells may be associated with the RUNX1 and PTEN pathways. Moreover, we showed that observed dysregulation could be associated with expression. We conclude that phenotypic changes in fibroblast responses to co-culturing with cancer epithelium result from orchestrated dysregulation of signaling pathways that favor their transformation and motility rather than proinflammatory status. This dysregulation can be observed both at the TF and transcriptome levels.]]>
Wed, 31 Dec 1969 19:00:00 EST
Chicken cecal DNA methylome alteration in the response to Salmonella enterica serovar Enteritidis inoculation. Wang Y, Liu L, Li M, Lin L, Su P, Tang H, Fan X, Li X
BMC Genomics (Nov 2020)

Salmonella enterica serovar Enteritidis (SE) is one of the pathogenic bacteria, which affects poultry production and poses a severe threat to public health. Chicken meat and eggs are the main sources of human salmonellosis. DNA methylation is involved in regulatory processes including gene expression, chromatin structure and genomic imprinting. To understand the methylation regulation in the response to SE inoculation in chicken, the genome-wide DNA methylation profile following SE inoculation was analyzed through whole-genome bisulfite sequencing in the current study.]]>
Wed, 31 Dec 1969 19:00:00 EST
Comparative genome-wide DNA methylation analysis in myocardial tissue from donors with and without Down syndrome. Cejas RB, Wang J, Hageman-Blair R, Liu S, Blanco JG
Gene (Jan 2021)

Down syndrome (DS, trisomy 21) is the most common major chromosomal aneuploidy compatible with life. The additional whole or partial copy of chromosome 21 results in genome-wide imbalances that drive the complex pathobiology of DS. Differential DNA methylation in the context of trisomy 21 may contribute to the variable architecture of the DS phenotype. The goal of this study was to examine the genomic DNA methylation landscape in myocardial tissue from non-fetal individuals with DS. >480,000 unique CpG sites were interrogated in myocardial DNA samples from individuals with (n = 12) and without DS (n = 12) using DNA methylation arrays. A total of 93 highly differentially methylated CpG sites and 16 differentially methylated regions were identified in myocardial DNA from subjects with DS. There were 18 differentially methylated CpG sites in chromosome 21, including 5 highly differentially methylated sites. A CpG site in the RUNX1 locus was differentially methylated in DS myocardium, and linear regression suggests that donors' age, gender, DS status, and RUNX1 methylation may contribute up to ~51% of the variability in RUNX1 mRNA expression. In DS myocardium, only 58% of the genes overlapping with differentially methylated regions codify for proteins with known functions and 24% are non-coding RNAs. This study provides an initial snapshot on the extent of genome-wide differential methylation in myocardial tissue from persons with DS.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genome-wide identification of imprinted genes in pigs and their different imprinting status compared with other mammals. Wu YQ, Zhao H, Li YJ, Khederzadeh S, Wei HJ, Zhou ZY, Zhang YP
Zool Res (Nov 2020)

Genomic imprinting often results in parent-of-origin specific differential expression of maternally and paternally inherited alleles and plays an essential role in mammalian development and growth. Mammalian genomic imprinting has primarily been studied in mice and humans, with only limited information available for pigs. To systematically characterize this phenomenon and evaluate imprinting status between different species, we investigated imprinted genes on a genome-wide scale in pig brain tissues. Specifically, we performed bioinformatics analysis of high-throughput sequencing results from parental genomes and offspring transcriptomes of hybrid crosses between Duroc and Diannan small-ear pigs. We identified 11 paternally and five maternally expressed imprinted genes in pigs with highly stringent selection criteria. Additionally, we found that the and genes, which are related to development, displayed a different imprinting status in pigs compared with that in mice and humans. This comprehensive research should help improve our knowledge on genomic imprinting in pigs and highlight the potential use of imprinted genes in the pig breeding field.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetic Assays in Purified Cardiomyocyte Nuclei. Hill MC, Martin JF
Methods Mol Biol (2021)

The adult mammalian heart's potential for regeneration is very inefficient. Importantly, adult mammalian cardiomyocytes (CMs) are characterized as a cell population with very limited mitotic potential. Conversely, the neonatal mouse heart possesses a brief, yet robust, regenerative capacity within the first week of life. Cell type-specific enrichment procedures are essential for characterizing the full spectrum of epigenomic landscapes and gene regulatory networks deployed by mammalian CMs. In this chapter, we describe a protocol useful for purifying CM nuclei from mammalian cardiac tissue. Furthermore, we detail a low-input procedure suitable for the parallel genome-wide profiling of chromatin accessibility, histone modifications, and transcription factor-binding sites. The CM nuclei purified using this process are suitable for multi-omic profiling approaches.]]>
Wed, 31 Dec 1969 19:00:00 EST
Predictive modeling of single-cell DNA methylome data enhances integration with transcriptome data. Uzun Y, Wu H, Tan K
Genome Res (Nov 2020)

Single-cell DNA methylation data has become increasingly abundant and has uncovered many genes with a positive correlation between expression and promoter methylation, challenging the common dogma based on bulk data. However, computational tools for analyzing single-cell methylome data are lagging far behind. A number of tasks, including cell type calling and integration with transcriptome data, requires the construction of a robust gene activity matrix as the prerequisite but challenging task. The advent of multi-omics data enables measurement of both DNA methylation and gene expression for the same single cells. Although such data is rather sparse, they are sufficient to train supervised models that capture the complex relationship between DNA methylation and gene expression and predict gene activities at single-cell level. Here, we present MAPLE (Methylome Association by Predictive Linkage to Expression), a computational framework that learns the association between DNA methylation and expression using both gene- and cell-dependent statistical features. Using multiple datasets generated with different experimental protocols, we show that using predicted gene activity values significantly improves several analysis tasks, including clustering, cell type identification and integration with transcriptome data. Application of MAPLE revealed several interesting biological insights into the relationship between methylation and gene expression, including asymmetric importance of methylation signals around transcription start site for predicting gene expression; and increased predictive power of methylation signals in promoters located outside CpG islands and shores. With the rapid accumulation of single-cell epigenomics data, MAPLE provides a general framework for integrating such data with transcriptome data.]]>
Wed, 31 Dec 1969 19:00:00 EST
Integrated Analysis of DNA Methylation, Hydroxymethylation, and Gene Expression Data Using ME-Class2. Singh MK, Edwards JR
Methods Mol Biol (2021)

There is increasing interest in understanding the pathological role of DNA methylation changes in disease by profiling genome-wide methylation changes. This includes both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The typical profiling study is designed to measure 5mC and/or 5hmC levels alongside gene expression in a set of samples and controls to determine a list of candidate genes whose 5mC and/or 5hmC changes are associated with expression changes. We recently showed that ME-Class2 substantially outperforms other bioinformatic approaches at accurately identify genes with highly associated methylation and expression changes. ME-Class2 further illuminated how synergistic changes in 5mC and 5hmC potentially contribute to gene silencing and activation. Here we present a detailed protocol for using ME-Class2 to analyze genome-wide methylation (5mC and/or 5hmC) and expression data. Further, we provide advice about extending ME-Class2 to study the relationships between other epigenetic marks.]]>
Wed, 31 Dec 1969 19:00:00 EST
EpiMogrify Models H3K4me3 Data to Identify Signaling Molecules that Improve Cell Fate Control and Maintenance. Kamaraj US, Chen J, Katwadi K, Ouyang JF, Yang Sun YB, Lim YM, Liu X, Handoko L, Polo JM, Petretto E, Rackham OJL
Cell Syst (Nov 2020)

The need to derive and culture diverse cell or tissue types in vitro has prompted investigations on how changes in culture conditions affect cell states. However, the identification of the optimal conditions (e.g., signaling molecules and growth factors) required to maintain cell types or convert between cell types remains a time-consuming task. Here, we developed EpiMogrify, an approach that leverages data from ∼100 human cell/tissue types available from ENCODE and Roadmap Epigenomics consortia to predict signaling molecules and factors that can either maintain cell identity or enhance directed differentiation (or cell conversion). EpiMogrify integrates protein-protein interaction network information with a model of the cell's epigenetic landscape based on H3K4me3 histone modifications. Using EpiMogrify-predicted factors for maintenance conditions, we were able to better potentiate the maintenance of astrocytes and cardiomyocytes in vitro. We report a significant increase in the efficiency of astrocyte and cardiomyocyte differentiation using EpiMogrify-predicted factors for conversion conditions.]]>
Wed, 31 Dec 1969 19:00:00 EST
Mapping DNA Methylation in Mammals: The State of the Art. Lentini A, Nestor CE
Methods Mol Biol (2021)

A complete understanding of the dynamics and function of cytosine modifications in mammalian biology is lacking. Central to achieving this understanding is the availability of techniques that permit sensitive and specific genome-wide mapping of DNA modifications in mammalian DNA. The last decade has seen the development of a vast arsenal of novel profiling approaches enabling epigeneticists to tackle research questions that were previously out of reach. Here, we review the techniques currently available for profiling DNA modifications in mammals, discuss their strengths and weaknesses, and speculate on the future direction of DNA modification profiling technologies.]]>
Wed, 31 Dec 1969 19:00:00 EST
Relative mRNA and protein stability of epigenetic regulators in musculoskeletal cell culture models. Badreldin AA, Bagheri L, Zhang B, Larson AN, van Wijnen AJ
Gene (Jan 2021)

Control of gene expression by epigenetic regulators is fundamental to tissue development and homeostasis. Loss-of-function (LOF) studies using siRNAs for epigenetic regulators require that RNA interference rapidly reduces the cellular levels of the corresponding mRNAs and/or proteins. The most abundant chromatin structural proteins (i.e., the core histones H2A, H2B, H3 and H4) have relatively long half-lives and do not turn over rapidly, although their mRNAs are labile. The question arises whether epigenetic regulatory enzymes (e.g., Ezh2) or proteins that interact with histones via selective modifications (e.g., Cbx1 to Cbx8, Brd4) are stable or unstable. Therefore, we performed classical α-amanitin and cycloheximide inhibition assays that block, respectively, mRNA transcription and protein translation in mouse MC3T3 osteoblasts, ATDC5 chondrocytes and C2C12 myoblasts. We find that mRNA levels of Cbx proteins and Ezh2 were significantly depleted after 24 hrs, while their corresponding proteins remained relatively stable. As positive control, the half-life of the labile cyclin D1 protein was found to be less than 1 hr. Our study suggests that histone code readers and writers are relatively stable chromatin-related proteins, which is consistent with their long-term activities in maintaining chromatin organization and phenotype identity. These findings have conceptual ramifications for the interpretation of RNAi experiments that reduce the mRNA but not protein levels of epiregulatory proteins. We propose that siRNAs for at least some epigenetic regulatory proteins may exert their biological effects by blocking translation and new protein synthesis rather than by decreasing pre-existing protein pools.]]>
Wed, 31 Dec 1969 19:00:00 EST
Profiling Chromatin Landscape at High Resolution and Throughput with 2C-ChIP. Wang XQD, Cameron CJF, Segal D, Paquette D, Blanchette M, Dostie J
Methods Mol Biol (2021)

Chromatin immunoprecipitation (ChIP) is used to probe the presence of proteins and/or their posttranslational modifications on genomic DNA. This method is often used alongside chromosome conformation capture approaches to obtain a better-rounded view of the functional relationship between chromatin architecture and its landscape. Since the inception of ChIP, its protocol has been modified to improve speed, sensitivity, and specificity. Combining ChIP with deep sequencing has recently improved its throughput and made genome-wide profiling possible. However, genome-wide analysis is not always the best option, particularly when many samples are required to study a given genomic region or when quantitative data is desired. We recently developed carbon copy-ChIP (2C-ChIP), a new form of the high-throughput ChIP analysis method ideally suited for these types of studies. 2C-ChIP applies ligation-mediated amplification (LMA) followed by deep sequencing to quantitatively detect specified genomic regions in ChIP samples. Here, we describe the generation of 2C-ChIP libraries and computational processing of the resulting sequencing data.]]>
Wed, 31 Dec 1969 19:00:00 EST
The Role of Epigenetics in the Reproductive Toxicity of Environmental Endocrine Disruptors. Shi Y, Qi W, Xu Q, Wang Z, Cao X, Zhou L, Ye L
Environ Mol Mutagen (Nov 2020)

Environmental endocrine disruptors (EEDs) seriously endanger human health by interfering with the normal function of reproductive systems. In males, EEDs can affect sperm formation and semen quality as well spermatogenesis, ultimately reducing fertility. In females, EEDs can affect uterine development and the expression levels of reproduction-related genes, ultimately reducing female fertility and the normal development of the fetus. There are a large number of putative mechanisms by which EEDs can induce reproductive toxicity, and many studies have shown the involvement of epigenetics. In this review, we summarize the role of DNA methylation, non-coding RNAs, genomic imprinting, chromatin remodeling and histone modification in the reproductive toxicity of EEDs. This article is protected by copyright. All rights reserved.]]>
Wed, 31 Dec 1969 19:00:00 EST
Developmental abnormalities and epigenetic alterations in medaka (Oryzias latipes) embryos induced by triclosan exposure. Song X, Wang X, Bhandari RK
Chemosphere (Dec 2020)

Triclosan (TCS), an antibacterial and antifungal agent present in some consumer products, has been detected in the environment at varying concentrations. TCS exposure has been found to cause developmental abnormalities and endocrine disruption in various species of fish. It is not clearly understood whether TCS exposure causes epigenetic alterations in developing embryos and their germ cells. In the present study, we examined the effects of TCS exposure (0, 50, 100 and, 200 μg/L) on embryonic development and primordial germ cells (PGCs), which are precursors of sperm and eggs, in medaka (Oyzias latipes). Developmental TCS exposure from 8 h post-fertilization through 15 days post-fertilization (dpf) resulted in several developmental abnormalities, including enlarged yolk sac, decreased head trunk angle (HTA), and severe edema in the pericardial region. The male ratio increased in the 100 μg/L TCS exposure group, which was negatively correlated with the expression of cyp19ala (a gene encoding aromatase) and arα (androgen receptor alpha). Developmental 50 μg/L TCS exposure resulted in global hypomethylation in the whole body but not in the isolated PGCs. Expression of the gene encoding DNA methyltransferases (dnmt1 and dnmt3aa) was decreased by 50 μg/L TCS exposure both in the whole body and PGCs. TCS altered the expression of genes encoding enzymes involved in DNA methylation and demethylation in PGCs, suggesting epigenetic effects on germ cells. The present results demonstrate that the embryos exposed to the tested concentrations of TCS develop deformities during the early life stages and that the TCS within this range possesses endocrine disrupting properties potential enough to alter sex ratios of developing embryos.]]>
Wed, 31 Dec 1969 19:00:00 EST
A pitfall for machine learning methods aiming to predict across cell types. Schreiber J, Singh R, Bilmes J, Noble WS
Genome Biol (Nov 2020)

Machine learning models that predict genomic activity are most useful when they make accurate predictions across cell types. Here, we show that when the training and test sets contain the same genomic loci, the resulting model may falsely appear to perform well by effectively memorizing the average activity associated with each locus across the training cell types. We demonstrate this phenomenon in the context of predicting gene expression and chromatin domain boundaries, and we suggest methods to diagnose and avoid the pitfall. We anticipate that, as more data becomes available, future projects will increasingly risk suffering from this issue.]]>
Wed, 31 Dec 1969 19:00:00 EST
Comparative epigenetics in animal physiology: An emerging frontier. Navarro-Martín L, Martyniuk CJ, Mennigen JA
Comp Biochem Physiol Part D Genomics Proteomics (Dec 2020)

The unprecedented access to annotated genomes now facilitates the investigation of the molecular basis of epigenetic phenomena in phenotypically diverse animals. In this critical review, we describe the roles of molecular epigenetic mechanisms in regulating mitotically and meiotically stable spatiotemporal gene expression, phenomena that provide the molecular foundation for the intra-, inter-, and trans-generational emergence of physiological phenotypes. By focusing principally on emerging comparative epigenetic roles of DNA-level and transcriptome-level epigenetic mark dynamics in the emergence of phenotypes, we highlight the relationship between evolutionary conservation and innovation of specific epigenetic pathways, and their interplay as a priority for future study. This comparative approach is expected to significantly advance our understanding of epigenetic phenomena, as animals show a diverse array of strategies to epigenetically modify physiological responses. Additionally, we review recent technological advances in the field of molecular epigenetics (single-cell epigenomics and transcriptomics and editing of epigenetic marks) in order to (1) investigate environmental and endogenous factor dependent epigenetic mark dynamics in an integrative manner; (2) functionally test the contribution of specific epigenetic marks for animal phenotypes via genome and transcript-editing tools. Finally, we describe advantages and limitations of emerging animal models, which under the Krogh principle, may be particularly useful in the advancement of comparative epigenomics and its potential translational applications in animal science, ecotoxicology, ecophysiology, climate change science and wild-life conservation, as well as organismal health.]]>
Wed, 31 Dec 1969 19:00:00 EST
Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors. Pignata L, Palumbo O, Cerrato F, Acurzio B, de Ãlava E, Roma J, Gallego S, Mora J, Carella M, Riccio A, Verde G
Cancers (Basel) (Nov 2020)

The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children's malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15.5 region. Multiple imprinted methylation alterations dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, raising the question of whether multiple imprinted loci were also affected in WT. To address this issue, we analyzed DNA methylation and chromosome profiles of 7 imprinted loci in 48 WT samples. The results demonstrated that methylation abnormalities of multiple imprinted loci occurred in 35% of the cases, but that they were associated with either chromosome aberrations or normal chromosome profiles. Multiple imprinted methylation changes were correlated with tumor stage and presence of metastasis, indicating that these epimutations were more frequent in highly aggressive tumors. When chromosome profiles were affected, these alterations were extended to flanking cancer driver genes. Overall, this study demonstrates the presence of multiple imprinted methylation defects in aggressive WTs and suggests that the mechanism by which they arise in embryonal and adult cancers is different.]]>
Wed, 31 Dec 1969 19:00:00 EST
Transcriptome dynamics of CD4 T cells during malaria maps gradual transit from effector to memory. Soon MSF, Lee HJ, Engel JA, Straube J, Thomas BS, Pernold CPS, Clarke LS, Laohamonthonkul P, Haldar RN, Williams CG, Lansink LIM, Moreira ML, Bramhall M, Koufariotis LT, Wood S, Chen X, James KR, Lönnberg T, Lane SW, Belz GT, Engwerda CR, Khoury DS, Davenport MP, Svensson V, Teichmann SA, Haque A
Nat Immunol (Dec 2020)

The dynamics of CD4 T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4 T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (T1) and follicular helper T (T) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T1 and T trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T and central memory were revealed, with antimalarials modulating these responses and boosting T1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4 T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene-gene correlations ( http://haquelab.mdhs.unimelb.edu.au/cd4_memory/ ).]]>
Wed, 31 Dec 1969 19:00:00 EST
The role of ZFP57 and additional KRAB-zinc finger proteins in the maintenance of human imprinted methylation and multi-locus imprinting disturbances. Monteagudo-Sánchez A, Hernandez Mora JR, Simon C, Burton A, Tenorio J, Lapunzina P, Clark S, Esteller M, Kelsey G, López-Siguero JP, de Nanclares GP, Torres-Padilla ME, Monk D
Nucleic Acids Res (11 2020)

Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation that is resistant to embryonic reprogramming, resulting in parental origin-specific monoallelic gene expression. A subset of individuals affected by imprinting disorders (IDs) displays multi-locus imprinting disturbances (MLID), which may result from aberrant establishment of imprinted differentially methylated regions (DMRs) in gametes or their maintenance in early embryogenesis. Here we investigated the extent of MLID in a family harbouring a ZFP57 truncating variant and characterize the interactions between human ZFP57 and the KAP1 co-repressor complex. By ectopically targeting ZFP57 to reprogrammed loci in mouse embryos using a dCas9 approach, we confirm that ZFP57 recruitment is sufficient to protect oocyte-derived methylation from reprogramming. Expression profiling in human pre-implantation embryos and oocytes reveals that unlike in mice, ZFP57 is only expressed following embryonic-genome activation, implying that other KRAB-zinc finger proteins (KZNFs) recruit KAP1 prior to blastocyst formation. Furthermore, we uncover ZNF202 and ZNF445 as additional KZNFs likely to recruit KAP1 to imprinted loci during reprogramming in the absence of ZFP57. Together, these data confirm the perplexing link between KZFPs and imprint maintenance and highlight the differences between mouse and humans in this respect.]]>
Wed, 31 Dec 1969 19:00:00 EST
Role of DNA methylation in the chromium tolerance of Scenedesmus acutus (Chlorophyceae) and its impact on the sulfate pathway regulation. Ferrari M, Torelli A, Marieschi M, Cozza R
Plant Sci (Dec 2020)

DNA methylation is a very important epigenetic modification that participates in many biological functions. Although many researches on DNA methylation have been reported in various plant species, few studies have assessed the global DNA methylation pattern in algae. Even more the complex mechanisms by which DNA methylation modulates stress in algae are yet largely unresolved, mainly with respect to heavy metal stress, for which in plants, metal- and species- specific responses were instead evidenced. In this work, we performed a comparative Whole-Genome Bisulfite Sequencing (WGBS) on two strains of the green alga Scenedesmus acutus with different Cr(VI) sensitivity. The pattern of distribution of 5-mC showed significant differences between the two strains concerning both differentially methylated local contexts (CG, CHG and CHH) and Differentially Methylated Regions (DMRs) as well. We also demonstrated that DNA methylation plays an important role in modulating some genes for sulfate uptake/assimilation confirming the involvement of the sulfate pathway in the Cr-tolerance. Our results suggest that DNA methylation may be of particular importance in defining signal specificity associated with Cr-tolerance and in establishing new epigenetic marks which contribute to the adaptation to metal stress and also to transmit the epigenomic traits to the progeny.]]>
Wed, 31 Dec 1969 19:00:00 EST
Brain-specific monoallelic expression of bovine UBE3A is associated with genomic position. Li J, Zhang C, Si H, Gu S, Liu X, Li D, Meng S, Yang X, Li S
Anim Genet (Nov 2020)

Genomic imprinting is a rare epigenetic process in mammalian cells that leads to monoallelic expression of a gene with a parent-specific pattern. The UBE3A (ubiquitin protein ligase E3A) gene is imprinted with maternal allelic expression in the brain but biallelically expressed in all other tissues in humans. The silencing of the paternal UBE3A allele is thought to be caused by the paternally expressed antisense RNA transcript of UBE3A-ATS. The aberrant imprinted expression of the UBE3A is associated with several neurodevelopmental syndromes and psychological disorders. Cattle are a valuable model species in determining the genetic etiology of sporadic human disorder, and maternal expression of UEB3A has been revealed by next-generation sequencing study in the bovine conceptus. In this study, we investigated the allelic expression of UBE3A and UBE3A-ATS in adult bovine somatic tissues. To confirm the splicing pattern of bovine UBE3A, five 5' alternative transcripts (MT210534-MT210538) were first obtained from bovine brain tissue by RT-PCR. Based on 10 SNP genotypes, we found that the brain-specific monoallelic expression of bovine UBE3A did not occur along the entire locus, and there was a shift from biallelic expression to monoallelic expression in exon 14 of the UBE3A gene. However, the brain-specific monoallelic expression of bovine UBE3A-ATS occurred in the entire gene. These observations demonstrated that the monoallelic expression did not occur along the bovine UBE3A entire locus and was associated with the genomic position.]]>
Wed, 31 Dec 1969 19:00:00 EST