'; ?> 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 Tue, 25 Sep 2018 10:53:48 EDT Tue, 25 Sep 2018 10:53:48 EDT jirtle@radonc.duke.edu james001@jirtle.com Parent of origin gene expression in a founder population identifies two new candidate imprinted genes at known imprinted regions. Mozaffari SV, Stein MM, Magnaye KM, Nicolae DL, Ober C
PLoS One (2018)

Genomic imprinting is the phenomena that leads to silencing of one copy of a gene inherited from a specific parent. Mutations in imprinted regions have been involved in diseases showing parent of origin effects. Identifying genes with evidence of parent of origin expression patterns in family studies allows the detection of more subtle imprinting. Here, we use allele specific expression in lymphoblastoid cell lines from 306 Hutterites related in a single pedigree to provide formal evidence for parent of origin effects. We take advantage of phased genotype data to assign parent of origin to RNA-seq reads in individuals with gene expression data. Our approach identified known imprinted genes, two putative novel imprinted genes, PXDC1 and PWAR6, and 14 genes with asymmetrical parent of origin gene expression. We used gene expression in peripheral blood leukocytes (PBL) to validate our findings, and then confirmed imprinting control regions (ICRs) using DNA methylation levels in the PBLs.]]>
Wed, 31 Dec 1969 19:00:00 EST
Whole-genome methylation profiling from PBMCs in acute-exacerbation COPD patients with good and poor responses to corticosteroid treatment. Lee SW, Hwang HH, Hsu PW, Chuang TY, Liu CW, Wu LS
Genomics (Sep 2018)

Identifying heterogeneity in chronic obstructive pulmonary disease (COPD) phenotypes is important for the development of personalized medicine. Genome-wide analysis was used to compare the methylation levels of peripheral blood mononuclear cell (PBMC) samples from 24 acute-exacerbation (AE) COPD patients with good/poor response to corticosteroid therapy and 12 non-COPD controls. Pyrosequencing was employed to validate the genome-wide analysis. In the dataset specific to COPD patients with a good response, enrichment was identified for the following: genes in the Ubl conjugation pathway, nicotinamide nucleotide metabolism, the alkaloid metabolic process, and regulation of the glucose metabolic process. Validation results confirmed CpG sites in PRKAG2 with different methylation levels in COPD patients and normal subjects. The CpG sites of ALOX5AP were specifically associated with a good response. The results suggested that a good response to corticosteroid treatment for AE-COPD should be considered a distinct subtype according to the putative epigenetic mechanism.]]>
Wed, 31 Dec 1969 19:00:00 EST
Beckwith-Wiedemann syndrome: clinical and etiopathogenic aspects of a model genomic imprinting entity. Cammarata-Scalisi F, Avendaño A, Stock F, Callea M, Sparago A, Riccio A
Arch Argent Pediatr (Oct 2018)

The Beckwith-Wiedemann syndrome is the most common genetic entity in overgrowth, with an approximate incidence of 1 in 10 00013 700births. Its broad clinical spectrum includes pre- and postnatal macrosomia, macroglossia, pinna abnormalities, abdominal wall defects, visceromegaly, and hyperinsulinemic hypoglycemia. This syndrome predisposes to childhood cancer and is caused by diverse genetic and/or epigenetic disorders that usually affect the regulation of genes imprinted on chromosome 11p15.5. The knowledge of (epi) genotype-phenotype correlations has prompted recommendations to propose different health care strategies, including tumor surveillance protocols based on molecular classification, aimed at standardizing clinical practice. The objective of this article is to describe the current status of the Beckwith-Wiedemann syndrome, a model of genomic imprinting.]]>
Wed, 31 Dec 1969 19:00:00 EST
Impacts of bisphenol A (BPA) and phthalate exposures on epigenetic outcomes in the human placenta. Strakovsky RS, Schantz SL
Environ Epigenet (Jul 2018)

The placenta guides fetal growth and development. Bisphenol A (BPA) and phthalates are widespread environmental contaminants and endocrine disruptors, and the placental epigenetic response to these chemicals is an area of growing research interest. Therefore, our objective was to summarize research linking BPA or phthalate exposure to placental outcomes in human pregnancies, with a particular focus on epigenetic endpoints. In PubMed, studies were selected for review (without limiting start date and ending on 1 May 2018) if they reported any direct effects of BPA or phthalates on the placenta in humans. Collectively, available studies suggest that BPA and phthalate exposures are associated with changes to placental micro-RNA expression, DNA methylation, and genomic imprinting. Furthermore, several studies suggest that fetal sex may be an important modifier of placental outcomes in response to these chemicals. Studies in humans demonstrate associations of BPA and phthalate exposure with adverse placental outcomes. Moving forward, more studies should consider sex differences (termed "placental sex") in the measured outcomes, and should utilize appropriate statistical approaches to assess modification by fetal sex. Furthermore, more consistent sample collection and molecular outcome assessment paradigms will be indispensable for making progress in the field. These advances, together with improved non-invasive tools for measuring placental function and outcomes across pregnancy, will be critical for understanding the mechanisms driving placental epigenetic disruption in response to BPA and phthalates, and how these disruptions translate into placental and fetal health.]]>
Wed, 31 Dec 1969 19:00:00 EST
Long noncoding RNAs: regulation, function and cancer. Rafiee A, Riazi-Rad F, Havaskary M, Nuri F
Biotechnol Genet Eng Rev (Oct 2018)

Long noncoding RNAs (lncRNAs) are non-protein-coding RNA transcripts that exert a key role in many cellular processes and have potential toward addressing disease etiology. Here, we review existing noncoding RNA classes and then describe a variety of mechanisms and functions by which lncRNAs regulate gene expression such as chromatin remodeling, genomic imprinting, gene transcription and post-transcriptional processing. We also examine several lncRNAs that contribute significantly to pathogenesis, oncogenesis, tumor suppression and cell cycle arrest of diverse cancer types and also give a summary of the pathways that lncRNAs might be involved in.]]>
Wed, 31 Dec 1969 19:00:00 EST
GENEASE: real time bioinformatics tool for multi-omics and disease ontology exploration, analysis and visualization. Ghandikota S, Hershey GKK, Mersha TB
Bioinformatics (Sep 2018)

Advances in high-throughput sequencing technologies have made it possible to generate multiple omics data at an unprecedented rate and scale. The accumulation of these omics data far outpaces the rate at which biologists can mine and generate new hypothesis to test experimentally. There is an urgent need to develop a myriad of powerful tools to efficiently and effectively search and filter these resources to address specific post-GWAS functional genomics questions. However, to date, these resources are scattered across several databases and often lack a unified portal for data annotation and analytics. In addition, existing tools to analyze and visualize these databases are highly fragmented, resulting researchers to access multiple applications and manual interventions for each gene or variant in an ad hoc fashion until all the questions are answered.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetics and Epigenomics: Implications for Diabetes and Obesity. Rosen ED, Kaestner KH, Natarajan R, Patti ME, Sallari R, Sander M, Susztak K
Diabetes (Oct 2018)

The American Diabetes Association convened a research symposium, "Epigenetics and Epigenomics: Implications for Diabetes and Obesity" on 17-19 November 2017. International experts in genetics, epigenetics, computational biology, and physiology discussed the current state of understanding of the relationships between genetics, epigenetics, and environment in diabetes and examined existing evidence for the role of epigenetic factors in regulating metabolism and the risk of diabetes and its complications. The authors summarize the presentations, which highlight how the complex interactions between genes and environment may in part be mediated through epigenetic changes and how information about nutritional and other environmental stimuli can be transmitted to the next generation. In addition, the authors present expert consensus on knowledge gaps and research recommendations for the field.]]>
Wed, 31 Dec 1969 19:00:00 EST
Multiomic Medulloblastomas. Rahmann EP, Gilbertson RJ
Cancer Cell (Sep 2018)

Epigenomics and transcriptomics of medulloblastoma-an important childhood brain tumor-segregate the disease into four clinically relevant subtypes. In this issue of Cancer Cell, Archer et al. and Forget et al. add the proteome to our multiomic map of this disease, revealing posttranscriptional and posttranslational variations with potential therapeutic implications.]]>
Wed, 31 Dec 1969 19:00:00 EST
Maintenance of grafting-induced epigenetic variations in the asexual progeny of Brassica oleracea and B. juncea chimera. Yu N, Cao L, Yuan L, Zhi X, Chen Y, Gan S, Chen L
Plant J (Oct 2018)

Grafting-induced variations have been observed in many plant species, but the heritability of variation in progeny is not well understood. In our study, adventitious shoots from the C cell lineage of shoot apical meristem (SAM) grafting chimera TCC (where the origin of the outmost, middle and innermost cell layers, respectively, of SAM is designated by 'T' for tuber mustard and 'C' for red cabbage) were induced and identified as r-CCC (r = regenerated). To investigate the maintenance of grafting variations during cell propagation and regeneration, different generations of asexual progeny (r-CCCn, n = generation) were established through successive regeneration of axillary shoots from r-CCC. The fourth generation of r-CCC (r-CCC4) was selected to perform whole genome bisulfite sequencing for comparative analysis of hetero-grafting-induced global methylation changes relative to r-s-CCC4 (s = self-grafting). Increased CHH methylation levels and proportions were observed in r-CCC4, with substantial changes occurring in the repeat elements. Small RNA sequencing revealed 1135 specific small interfering RNA (siRNA) tags that were typically expressed in r-CCC, r-CCC2 and r-CCC4. Notably, 65% of these specific siRNAs were associated with repeat elements, termed RE siRNAs. Subsequent analysis revealed that the CHH methylation of RE siRNA-overlapping regions was mainly hypermethylation in r-CCC4, indicating that they were responsible for directing and maintaining grafting-induced CHH methylation. Moreover, the expression of 13 differentially methylated genes (DMGs) correlated with the phenotypic variation, showing differential expression levels between r-CCC4 and r-s-CCC4. These DMGs were predominantly CG hypermethylated, their methylation modifications corresponded to the transcription of relative methyltransferase.]]>
Wed, 31 Dec 1969 19:00:00 EST
Contemporary Trends Emerging in Epigenomics and Metabolism. El-Osta A
Antioxid Redox Signal (Oct 2018)

Diabetes is the disease of our time. It is a complex disorder. It is increasingly appreciated that genetic factors cannot fully explain susceptibility to diabetes and its complications. For almost a decade, the epigenetics field has grown tremendously becoming an alternative but integral component of how we interpret gene regulation. Some consider the field an epiphenomenon with an evidence base awaiting critical testing. The advent of experimental tools combined with the development of research methods has brought with the field technological advancements that allow scientists to assess ideas that have not yet been tested critically. If there was ever a time not to give up on epigenetics, then that time would be now. Under the seeming disorder of more than 3 billion base pairs, the human genome works successfully with order. It is a complex order. Instructed by a chemical code that is largely uncharted in metabolic disease, developmental studies have clearly shown that code exclusivity is key to unlocking the genetic blueprint. Central to this chemical code are specific modifications to DNA and RNA, histones and nonhistone proteins: these tiny chemical marks that have wide-ranging functions. Robustness is key, and these marks are written to be precisely read and accurately erased.]]>
Wed, 31 Dec 1969 19:00:00 EST
Predictive biomarkers for type 2 of diabetes mellitus: Bridging the gap between systems research and personalized medicine. Kraniotou C, Karadima V, Bellos G, Tsangaris GT
J Proteomics (Sep 2018)

The global incidence of metabolic disorders like type 2 diabetes mellitus (DM2) has assumed epidemic proportions, leading to adverse health and socio-economic impacts. It is therefore of critical importance the early diagnosis of DM2 patients and the detection of those at increased risk of disease. In this respect, Precision Medicine (PM) is an emerging approach that includes practices, tests, decisions and treatments adapted to the characteristics of each patient. With regard to DM2, PM manages a wealth of "omics" data (genomic, metabolic, proteomic, environmental, clinical and paraclinical) to increase the number of clinically validated biomarkers in order to identify patients in early stage even before the prediabetic phase.]]>
Wed, 31 Dec 1969 19:00:00 EST
The origin of imprinting defects in Temple syndrome and comparison with other imprinting disorders. Beygo J, Mertel C, Kaya S, Gillessen-Kaesbach G, Eggermann T, Horsthemke B, Buiting K
Epigenetics (Sep 2018)

Temple syndrome (TS14) is a rare imprinting disorder caused by genetic and epigenetic alterations on chromosome 14q32. A subset of these patients shows an imprinting defect (ID) where the paternal allele harbors a maternal epigenotype thus silencing the paternally expressed genes and leading to an increased expression of the maternally expressed genes. We investigated the grandparental origin of the incorrectly imprinted chromosome 14 in a cohort of 13 TS14 ID patients and their families. In seven families grandmaternal and, in six families, grandpaternal inheritance was observed. These results indicate that the ID occurred after imprint erasure in the paternal germ line. While the complete lack of methylation as observed in the majority of TS14 ID patients may be due to an imprint establishment error in the paternal germ line, cases with methylation mosaicism suggest that in general many IDs (TS14, AS, BWS, and SRS) are in fact of somatic origin in the early or late embryo.]]>
Wed, 31 Dec 1969 19:00:00 EST
Backbone and side-chain resonance assignments of the methyl-CpG-binding domain of MBD6 from Arabidopsis thaliana. Iwakawa N, Mahana Y, Ono A, Ohki I, Walinda E, Morimoto D, Sugase K, Shirakawa M
Biomol NMR Assign (Sep 2018)

Epigenetic regulation is essential to various biological phenomena such as cell differentiation and cancer. DNA methylation is one of the most important epigenetic signals, as it is directly involved in gene silencing of transposable elements, genomic imprinting, and chromosome X inactivation. To mediate these processes, methyl-CpG-binding domain (MBD) proteins recognize specific signals encoded in the form of DNA methylation patterns. AtMBD6, one of the 12 MBD proteins in Arabidopsis thaliana, shares a high sequential homology in the MBD domain with mammalian MBD proteins, but a detailed characterization of its structural and functional properties remains elusive. Here, we report the H, C, and N resonance assignments of the isolated MBD domain of AtMBD6. Analysis of the chemical shift data implied that the MBD domain of AtMBD6 has a secondary structure similar to that of mammalian MeCP2, while the β-strands β1 and β3 of AtMBD6 were found to be longer than those of MeCP2. The structural differences provide insight into the different recognition mechanisms of methylated DNA by plant and mammalian MBDs. The assignments reported here will aid further analyses such as titration experiments and three-dimensional structure determination using NMR to yield a detailed characterization of the interaction between AtMBD6 and methylated DNAs.]]>
Wed, 31 Dec 1969 19:00:00 EST
A tandem repeat array in IG-DMR is essential for imprinting of paternal allele at the Dlk1-Dio3 domain during embryonic development. Saito T, Hara S, Kato T, Tamano M, Muramatsu A, Asahara H, Takada S
Hum Mol Genet (Sep 2018)

Genomic imprinting is a phenomenon that causes parent-origin-specific monoallelic expression of a small subset of genes, known as imprinted genes, by parentally inherited epigenetic marks. Imprinted genes at the delta-like homolog 1 gene (Dlk1)-type III iodothyronine deiodinase gene (Dio3) imprinted domain, regulated by intergenic differentially methylated region (IG-DMR), are essential for normal development of late embryonic stages. Although the functions of IG-DMR have been reported by generating knockout mice, molecular details of the regulatory mechanisms are not fully understood as the specific sequence(s) of IG-DMR have not been identified. Here, we generated mutant mice by deleting a 216 bp tandem repeated sequence in IG-DMR, which comprised seven repeats of 24 bp motifs, by genome editing technologies. The mutant mice showed that paternal transmission of the deletion allele, but not maternal transmission, induces severe growth retardation and perinatal lethality, possibly due to placental defects. Embryos with a paternally transmitted deletion allele showed biallelic expression of maternally expressed genes and repression of paternally expressed genes. DNA methylation status also showed loss of methylation at IG-DMR and Gtl2-DMR, indicating that the tandem repeat sequence of IG-DMR is one of the functional sequences of IG-DMR, which is required for maintaining DNA methylation imprints of paternal allele at IG-DMR.]]>
Wed, 31 Dec 1969 19:00:00 EST
Biomarkers: paving stones on the road towards the personalized precision medicine for oral squamous cell carcinoma. Zhong L, Liu Y, Wang K, He Z, Gong Z, Zhao Z, Yang Y, Gao X, Li F, Wu H, Zhang S, Chen L
BMC Cancer (Sep 2018)

Traditional therapeutics have encountered a bottleneck caused by diagnosis delay and subjective and unreliable assessment. Biomarkers can overcome this bottleneck and guide us toward personalized precision medicine for oral squamous cell carcinoma. To achieve this, it is important to efficiently and accurately screen out specific biomarkers from among the huge number of molecules. Progress in omics-based high-throughput technology has laid a solid foundation for biomarker discovery. With credible and systemic biomarker models, more precise and personalized diagnosis and assessment would be achieved and patients would be more likely to be cured and have a higher quality of life. However, this is not straightforward owing to the complexity of molecules involved in tumorigenesis. In this context, there is a need to focus on tumor heterogeneity and homogeneity, which are discussed in detail. In this review, we aim to provide an understanding of biomarker discovery and application for precision medicine of oral squamous cell carcinoma, and have a strong belief that biomarker will pave the road toward future precision medicine.]]>
Wed, 31 Dec 1969 19:00:00 EST
Parallels between Mammalian Mechanisms of Monoallelic Gene Expression. Khamlichi AA, Feil R
Trends Genet (Sep 2018)

Different types of monoallelic gene expression are present in mammals, some of which are highly flexible, whereas others are more rigid. These include allelic exclusion at antigen receptor loci, the expression of olfactory receptor genes, genomic imprinting, X-chromosome inactivation, and random monoallelic expression (MAE). Although these processes play diverse biological roles, and arose through different selective pressures, the underlying epigenetic mechanisms show striking resemblances. Regulatory transcriptional events are important in all systems, particularly in the specification of MAE. Combined with comparative studies between species, this suggests that the different MAE systems found in mammals may have evolved from analogous ancestral processes.]]>
Wed, 31 Dec 1969 19:00:00 EST
Effects of maternal nutrition on the expression of genomic imprinted genes in ovine fetuses. Duan JE, Zhang M, Flock K, Seesi SA, Mandoiu I, Jones A, Johnson E, Pillai S, Hoffman M, McFadden K, Jiang H, Reed S, Govoni K, Zinn S, Jiang Z, Tian XC
Epigenetics (Sep 2018)

Genomic imprinting is an epigenetic phenomenon of differential allelic expression based on parental origin. To date, 263 imprinted genes have been identified among all investigated mammalian species. However, only 21 have been described in sheep, of which 11 are annotated in the current ovine genome. Here, we aim to i) use DNA/RNA high throughput sequencing to identify new monoallelically expressed and imprinted genes in day 135 ovine fetuses and ii) determine whether maternal diet (100%, 60%, or 140% of National Research Council Total Digestible Nutrients) influences expression of imprinted genes. We also reported strategies to solve technical challenges in the data analysis pipeline. We identified 80 monoallelically expressed, 13 new putative imprinted genes, and five known imprinted genes in sheep using the 263 genes stated above as a guide. Sanger sequencing confirmed allelic expression of seven genes, CASD1, COPG2, DIRAS3, INPP5F, PLAGL1, PPP1R9A, and SLC22A18. Among the 13 putative imprinted genes, five were localized in the known sheep imprinting domains of MEST on chromosome 4, DLK1/GTL2 on chromosome 18 and KCNQ1 on chromosome 21, and three were in a novel sheep imprinted cluster on chromosome 4, known in other species as PEG10/SGCE. The expression of DIRAS3, IGF2, PHLDA2, and SLC22A18 was altered by maternal diet, albeit without allelic expression reversal. Together, our results expanded the list of sheep imprinted genes to 34 and demonstrated that while the expression levels of four imprinted genes were changed by maternal diet, the allelic expression patterns were un-changed for all imprinted genes studied.]]>
Wed, 31 Dec 1969 19:00:00 EST
A Loss of Epigenetic Control Can Promote Cell Death through Reversing the Balance of Pathways in a Signaling Network. Vanaja KG, Timp W, Feinberg AP, Levchenko A
Mol Cell (Sep 2018)

Epigenetic control of regulatory networks is only partially understood. Expression of Insulin-like growth factor-II (IGF2) is controlled by genomic imprinting, mediated by silencing of the maternal allele. Loss of imprinting of IGF2 (LOI) is linked to intestinal and colorectal cancers, causally in murine models and epidemiologically in humans. However, the molecular underpinnings of the LOI phenotype are not clear. Surprisingly, in LOI cells, we find a reversal of the relative activities of two canonical signaling pathways triggered by IGF2, causing further rebalancing between pro- and anti-apoptotic signaling. A predictive mathematical model shows that this network rebalancing quantitatively accounts for the effect of receptor tyrosine kinase inhibition in both WT and LOI cells. This mechanism also quantitatively explains both the stable LOI phenotype and the therapeutic window for selective killing of LOI cells, and thus prevention of epigenetically controlled cancers. These findings suggest a framework for understanding epigenetically modified cell signaling.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genomic approaches for studying crop evolution. Schreiber M, Stein N, Mascher M
Genome Biol (Sep 2018)

Understanding how crop plants evolved from their wild relatives and spread around the world can inform about the origins of agriculture. Here, we review how the rapid development of genomic resources and tools has made it possible to conduct genetic mapping and population genetic studies to unravel the molecular underpinnings of domestication and crop evolution in diverse crop species. We propose three future avenues for the study of crop evolution: establishment of high-quality reference genomes for crops and their wild relatives; genomic characterization of germplasm collections; and the adoption of novel methodologies such as archaeogenetics, epigenomics, and genome editing.]]>
Wed, 31 Dec 1969 19:00:00 EST
Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development. Matoba S, Wang H, Jiang L, Lu F, Iwabuchi KA, Wu X, Inoue K, Yang L, Press W, Lee JT, Ogura A, Shen L, Zhang Y
Cell Stem Cell (Sep 2018)

Animal cloning can be achieved through somatic cell nuclear transfer (SCNT), although the live birth rate is relatively low. Recent studies have identified H3K9me3 in donor cells and abnormal Xist activation as epigenetic barriers that impede SCNT. Here we overcome these barriers using a combination of Xist knockout donor cells and overexpression of Kdm4 to achieve more than 20% efficiency of mouse SCNT. However, post-implantation defects and abnormal placentas were still observed, indicating that additional epigenetic barriers impede SCNT cloning. Comparative DNA methylome analysis of IVF and SCNT blastocysts identified abnormally methylated regions in SCNT embryos despite successful global reprogramming of the methylome. Strikingly, allelic transcriptomic and ChIP-seq analyses of pre-implantation SCNT embryos revealed complete loss of H3K27me3 imprinting, which may account for the postnatal developmental defects observed in SCNT embryos. Together, these results provide an efficient method for mouse cloning while paving the way for further improving SCNT efficiency.]]>
Wed, 31 Dec 1969 19:00:00 EST