'; ?> 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, 03 Sep 2015 02:06:35 PDT Thu, 03 Sep 2015 02:06:35 PDT jirtle@radonc.duke.edu james001@jirtle.com Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans. Docherty LE, Rezwan FI, Poole RL, Turner CL, Kivuva E, Maher ER, Smithson SF, Hamilton-Shield JP, Patalan M, Gizewska M, Peregud-Pogorzelski J, Beygo J, Buiting K, Horsthemke B, Soellner L, Begemann M, Eggermann T, Baple E, Mansour S, Temple IK, Mackay DJ
Nat Commun (2015)

Human-imprinting disorders are congenital disorders of growth, development and metabolism, associated with disturbance of parent of origin-specific DNA methylation at imprinted loci across the genome. Some imprinting disorders have higher than expected prevalence of monozygotic twinning, of assisted reproductive technology among parents, and of disturbance of multiple imprinted loci, for which few causative trans-acting mutations have been found. Here we report mutations in NLRP5 in five mothers of individuals affected by multilocus imprinting disturbance. Maternal-effect mutations of other human NLRP genes, NLRP7 and NLRP2, cause familial biparental hydatidiform mole and multilocus imprinting disturbance, respectively. Offspring of mothers with NLRP5 mutations have heterogenous clinical and epigenetic features, but cases include a discordant monozygotic twin pair, individuals with idiopathic developmental delay and autism, and families affected by infertility and reproductive wastage. NLRP5 mutations suggest connections between maternal reproductive fitness, early zygotic development and genomic imprinting.]]>
Tue, 01 Sep 2015 00:00:00 PDT
Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism. Hoffmann A, Spengler D
World J Biol Chem (Aug 2015)

Transient neonatal diabetes mellitus 1 (TNDM1) is a rare genetic disorder representing with severe neonatal hyperglycaemia followed by remission within one and a half year and adolescent relapse with type 2 diabetes in half of the patients. Genetic defects in TNDM1 comprise uniparental isodisomy of chromosome 6, duplication of the minimal TNDM1 locus at 6q24, or relaxation of genomically imprinted ZAC1/HYMAI. Whereas the function of HYMAI, a non-coding mRNA, is still unidentified, biochemical and molecular studies show that zinc finger protein 1 regulating apoptosis and cell cycle arrest (ZAC1) behaves as a factor with versatile transcriptional functions dependent on binding to specific GC-rich DNA motives and interconnected regulation of recruited coactivator activities. Genome-wide expression profiling enabled the isolation of a number of Zac1 target genes known to regulate different aspects of β-cell function and peripheral insulin sensitivity. Among these, upregulation of Pparγ and Tcf4 impairs insulin-secretion and β-cell proliferation. Similarly, Zac1-mediated upregulation of Socs3 may attenuate β-cell proliferation and survival by inhibition of growth factor signalling. Additionally, Zac1 directly represses Pac1 and Rasgrf1 with roles in insulin secretion and β-cell proliferation. Collectively, concerted dysregulation of these target genes could contribute to the onset and course of TNDM1. Interestingly, Zac1 overexpression in β-cells spares the effects of stimulatory G-protein signaling on insulin secretion and raises the prospect for tailored treatments in relapsed TNDM1 patients. Overall, these results suggest that progress on the molecular and cellular foundations of monogenetic forms of diabetes can advance personalized therapy in addition to deepening the understanding of insulin and glucose metabolism in general.]]>
Mon, 31 Aug 2015 00:00:00 PDT
Bromodomain-Containing Protein 4: The Epigenetic Origin of Pulmonary Arterial Hypertension. Meloche J, Potus F, Vaillancourt M, Bourgeois A, Johnson I, Deschamps L, Chabot S, Ruffenach G, Henry S, Breuils-Bonnet S, Tremblay Ãˆ, Nadeau V, Lambert C, Paradis R, Provencher S, Bonnet S
Circ Res (Aug 2015)

Pulmonary arterial hypertension (PAH) is a vasculopathy characterized by enhanced pulmonary artery (PA) smooth muscle cell (PASMC) proliferation and suppressed apoptosis. Decreased expression of microRNA-204 has been associated to this phenotype. By a still elusive mechanism, microRNA-204 downregulation promotes the expression of oncogenes, including nuclear factor of activated T cells, B-cell lymphoma 2, and Survivin. In cancer, increased expression of the epigenetic reader bromodomain-containing protein 4 (BRD4) sustains cell survival and proliferation. Interestingly, BRD4 is a predicted target of microRNA-204 and has binding sites on the nuclear factor of activated T cells promoter region.]]>
Fri, 28 Aug 2015 00:00:00 PDT
Expression of imprinted genes in placenta is associated with infant neurobehavioral development. Green BB, Kappil M, Lambertini L, Armstrong DA, Guerin DJ, Sharp AJ, Lester BM, Chen J, Marsit CJ
Epigenetics (Sep 2015)

Genomic imprinting disorders often exhibit delayed neurobehavioral development, suggesting this unique mechanism of epigenetic regulation plays a role in mental and neurological health. While major errors in imprinting have been linked to adverse health outcomes, there has been little research conducted on how moderate variability in imprinted gene expression within a population contributes to differences in neurobehavioral outcomes, particularly at birth. Here, we profiled the expression of 108 known and putative imprinted genes in human placenta samples from 615 infants assessed by the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scales (NNNS). Data reduction identified 10 genes (DLX5, DHCR24, VTRNA2-1, PHLDA2, NPAP1, FAM50B, GNAS-AS1, PAX8-AS1, SHANK2, and COPG2IT1) whose expression could distinguish between newborn neurobehavioral profiles derived from the NNNS. Clustering infants based on the expression pattern of these genes identified 2 groups of infants characterized by reduced quality of movement, increased signs of asymmetrical and non-optimal reflexes, and increased odds of demonstrating increased signs of physiologic stress and abstinence. Overall, these results suggest that common variation in placental imprinted gene expression is linked to suboptimal performance on scales of neurological functioning as well as with increased signs of physiologic stress, highlighting the central importance of the control of expression of these genes in the placenta for neurobehavioral development.]]>
Fri, 28 Aug 2015 00:00:00 PDT
Abnormal expression of DNA methyltransferases and genomic imprinting in cloned goat fibroblasts. Wan Y, Deng M, Zhang G, Ren C, Zhang H, Zhang Y, Wang L, Wang F
Cell Biol Int (Aug 2015)

Somatic cell nuclear transfer (SCNT) is a useful way to produce cloned animals. However, SCNT animals exhibit DNA methylation and genomic imprinting abnormalities. These abnormalities may due to the faulty epigenetic reprogramming of donor cells. To investigate the consequence of SCNT on the genomic imprinting and global methylation in the donor cells, growth patterns, and apoptosis of cloned goat fibroblast cells (CGFCs) at passage seven were determined. Growth patterns in CGFCs was similar to the controls, however, growth rate in log phase was lower and apoptosis in CGFCs was significantly higher (P < 0.01). In addition, quantitative expression analysis of three DNA methyltransferases (Dnmt) and two imprinted genes (H19, IGF2R) was conducted in CGFCs: Dnmt1 and Dnmt3b expression was significantly reduced (P < 0.01), and H19 expression was decreased sixfold (P < 0.01), however, the expression of Dnmt3a was unaltered and IGF2R expression was significantly increased (P < 0.05). Finally, we used bisulfite sequencing PCR to compare the DNA methylation patterns in differentially methylated regions (DMRs) of H19 and IGF2R. The DMRs of H19 (P < 0.01) and IGF2R (P < 0.01) were both highly methylated in CGFCs. These results indicate that the global genome might be hypomethylated. Moreover, there is aberrant expression of imprinted genes and DMR methylation in CGFCs.]]>
Fri, 28 Aug 2015 00:00:00 PDT
Derivation of a Homozygous Human Androgenetic Embryonic Stem Cell Line. Ding C, Huang S, Qi Q, Fu R, Zhu W, Cai B, Hong P, Liu Z, Gu T, Zeng Y, Wang J, Xu Y, Zhao X, Zhou Q, Zhou C
Stem Cells Dev (Aug 2015)

Human embryonic stem cells (hESCs) have long been considered as a promising source for cell replacement therapy. However, one major obstacle for the use of these cells is immune compatibility. Histocompatible human parthenogenetic ESCs have been reported as a new method for generating human leukocyte antigen (HLA)-matched hESCs. To further investigate the possibility of obtaining histocompatible stem cells from uniparental embryos, we tried to produce androgenetic haploid human embryos by injecting a single spermatozoon into enucleated human oocyte, and establish human androgenetic embryonic stem (hAGES) cell lines from androgenetic embryos. In the present study, a diploid hAGES cell line has been established, which exhibits typical features of human ESCs, including the expression of pluripotency markers, having differentiation potential in vitro and in vivo, and stable propagation in an undifferentiated state (>P40). Bisulfite sequencing of the H19, Snrpn, Meg3, and Kv imprinting control regions suggested that hAGES cells maintained to a certain extent a sperm methylation pattern. Genome-wide single nucleotide polymorphism, short tandem repeat, and HLA analyses revealed that the hAGES cell genome was highly homozygous. These results suggest that hAGES cells from spermatozoon could serve as a useful tool for studying the mechanisms underlying genomic imprinting in humans. It might also be used as a potential resource for cell replacement therapy as parthenogenetic stem cells.]]>
Mon, 24 Aug 2015 00:00:00 PDT
Speciation and reduced hybrid female fertility in house mice. Suzuki TA, Nachman MW
Evolution (Aug 2015)

In mammals, intrinsic postzygotic isolation has been well studied in males but has been less studied in females, despite the fact that female gametogenesis and pregnancy provide arenas for hybrid sterility or inviability that are absent in males. Here, we asked whether inviability or sterility is observed in female hybrids of Mus musculus domesticus and M. m. musculus, taxa which hybridize in nature and for which male sterility has been well characterized. We looked for parent-of-origin growth phenotypes by measuring adult body weights in F1 hybrids. We evaluated hybrid female fertility by crossing F1 females to a tester male and comparing multiple reproductive parameters between intra-subspecific controls and inter-subspecific hybrids. Hybrid females showed no evidence of parent-of-origin overgrowth or undergrowth, providing no evidence for reduced viability. However, hybrid females had smaller litter sizes, reduced embryo survival, fewer ovulations, and fewer small follicles relative to controls. Significant variation in reproductive parameters was seen among different hybrid genotypes, suggesting that hybrid incompatibilities are polymorphic within subspecies. Differences in reproductive phenotypes in reciprocal genotypes were observed and are consistent with cyto-nuclear incompatibilities or incompatibilities involving genomic imprinting. These findings highlight the potential importance of reduced hybrid female fertility in the early stages of speciation. This article is protected by copyright. All rights reserved.]]>
Mon, 24 Aug 2015 00:00:00 PDT
Toward understanding the evolution of vertebrate gene regulatory networks: comparative genomics and epigenomic approaches. Martinez-Morales JR
Brief Funct Genomics (Aug 2015)

Vertebrates, as most animal phyla, originated >500 million years ago during the Cambrian explosion, and progressively radiated into the extant classes. Inferring the evolutionary history of the group requires understanding the architecture of the developmental programs that constrain the vertebrate anatomy. Here, I review recent comparative genomic and epigenomic studies, based on ChIP-seq and chromatin accessibility, which focus on the identification of functionally equivalent cis-regulatory modules among species. This pioneer work, primarily centered in the mammalian lineage, has set the groundwork for further studies in representative vertebrate and chordate species. Mapping of active regulatory regions across lineages will shed new light on the evolutionary forces stabilizing ancestral developmental programs, as well as allowing their variation to sustain morphological adaptations on the inherited vertebrate body plan.]]>
Fri, 21 Aug 2015 00:00:00 PDT
Genomic Profiling Reveals Unique Molecular Alterations in Hepatoblastomas and Adjacent Hepatocellular Carcinomas in B6C3F1 Mice. Bhusari S, Pandiri AR, Nagai H, Wang Y, Foley J, Hong HL, Ton TV, DeVito M, Shockley KR, Peddada SD, Gerrish KE, Malarkey DE, Hooth MJ, Sills RC, Hoenerhoff MJ
Toxicol Pathol (Aug 2015)

The cell of origin of hepatoblastoma (HB) in humans and mice is unknown; it is hypothesized to be a transformed hepatocyte, oval cell, or hepatic progenitor cell. In mice, current dogma is that HBs arise from preexisting hepatocellular neoplasms as a result of further neoplastic transformation. However, there is little evidence supporting this direct relationship. To better understand the relationship between hepatocellular carcinoma (HCC) and HB and determine molecular similarities between mouse and human HB, global gene expression analysis and targeted mutation analysis were performed using HB, HCC, and adjacent liver from the same animals in a recent National Toxicology Program bioassay. There were significant differences in Hras and Ctnnb1 mutation spectra, and by microarray, HBs showed dysregulation of embryonic development, stem cell pluripotency, and genomic imprinting compared to HCC. Meta-analysis showed similarities between HB, early mouse embryonic liver, and hepatocyte-derived stem/progenitor cells compared to HCC. Our data show that there are striking differences between HB and HCC and suggest that HB is a significantly different entity that may arise from a hepatic precursor cell. Furthermore, mouse HB is similar to the human disease at the pathway level and therefore is likely a relevant model for evaluating human cancer hazard.]]>
Thu, 20 Aug 2015 00:00:00 PDT
Biomarkers in neonatology: the new "omics" of bronchopulmonary dysplasia. Piersigilli F, Bhandari V
J Matern Fetal Neonatal Med (Aug 2015)

Bronchopulmonary dysplasia (BPD) is a complex disorder resulting from gene-environmental interactions. An improved understanding of the pathogenesis of this most common chronic lung disease in infants has been made by utilizing animal models and correlating with human data. Currently, while some (vitamin A, caffeine) pharmacotherapeutic options are being utilized to ameliorate this condition, there is still no specific or effective treatment for BPD. It would be helpful for prognostication and targeted potential novel therapeutic strategies to identify those babies accurately who are at risk for developing this disease. A reliable biomarker would have the capacity to be detected in the initial phase of the disease, to allow early interventions to avoid or minimize the detrimental effects of the disease. This review will focus on human studies performed with the "omic" techniques, specifically genomics, epigenomics, microbiomics, transciptomics, proteomics and metabolomics, and summarize the information available in the literature, as it pertains to biomarker identification for BPD. Using "omics" technologies, investigators have reported markers that have the potential to be used as biomarkers of BPD: SPOCK2, VEGF -624C > G, VEGF -460T > C, mast cells specific markers, miR-219 pathway, miR-152, -30a-3p, -133b, -206, -7, lactate, taurine, trimethylamine-N-oxide, gluconate, myoinositol and alterations in surfactant lipid profile.]]>
Thu, 20 Aug 2015 00:00:00 PDT
Systematic chromatin state comparison of epigenomes associated with diverse properties including sex and tissue type. Yen A, Kellis M
Nat Commun (2015)

Epigenomic data sets provide critical information about the dynamic role of chromatin states in gene regulation, but a key question of how chromatin state segmentations vary under different conditions across the genome has remained unaddressed. Here we present ChromDiff, a group-wise chromatin state comparison method that generates an information-theoretic representation of epigenomes and corrects for external covariate factors to better isolate relevant chromatin state changes. By applying ChromDiff to the 127 epigenomes from the Roadmap Epigenomics and ENCODE projects, we provide novel group-wise comparative analyses across sex, tissue type, state and developmental age. Remarkably, we find that distinct sets of epigenomic features are maximally discriminative for different group-wise comparisons, in each case revealing distinct enriched pathways, many of which do not show gene expression differences. Our methodology should be broadly applicable for epigenomic comparisons and provides a powerful new tool for studying chromatin state differences at the genome scale.]]>
Tue, 18 Aug 2015 00:00:00 PDT
Reproductive mode and the shifting arenas of evolutionary conflict. Furness AI, Morrison KR, Orr TJ, Arendt JD, Reznick DN
Ann N Y Acad Sci (Aug 2015)

In sexually reproducing organisms, the genetic interests of individuals are not perfectly aligned. Conflicts among family members are prevalent since interactions involve the transfer of limited resources between interdependent players. Intrafamilial conflict has traditionally been considered along three major axes: between the sexes, between parents and offspring, and between siblings. In these interactions, conflict is expected over traits in which the resulting phenotypic value is determined by multiple family members who have only partially overlapping fitness optima. We focus on four major categories of animal reproductive mode (broadcast spawning, egg laying, live bearing, and live bearing with matrotrophy) and identify the shared phenotypes or traits over which conflict is expected, and then review the empirical literature for evidence of their occurrence. Major transitions among reproductive mode, such as a shift from external to internal fertilization, an increase in egg-retention time, modifications of embryos and mothers for nutrient transfer, the evolution of postnatal parental care, and increased interaction with the kin network, mark key shifts that both change and expand the arenas in which conflict is played out.]]>
Tue, 18 Aug 2015 00:00:00 PDT
Noncanonical Genomic Imprinting Effects in Offspring. Bonthuis PJ, Huang WC, Stacher Hörndli CN, Ferris E, Cheng T, Gregg C
Cell Rep (Aug 2015)

Here, we describe an RNA-sequencing (RNA-seq)-based approach that accurately detects even modest maternal or paternal allele expression biases at the tissue level, which we call noncanonical genomic imprinting effects. We profile imprinting in the arcuate nucleus (ARN) and dorsal raphe nucleus of the female mouse brain as well as skeletal muscle (mesodermal) and liver (endodermal). Our study uncovers hundreds of noncanonical autosomal and X-linked imprinting effects. Noncanonical imprinting is highly tissue-specific and enriched in the ARN, but rare in the liver. These effects are reproducible across different genetic backgrounds and associated with allele-specific chromatin. Using in situ hybridization for nascent RNAs, we discover that autosomal noncanonical imprinted genes with a tissue-level allele bias exhibit allele-specific expression effects in subpopulations of neurons in the brain in vivo. We define noncanonical imprinted genes that regulate monoamine signaling and determine that these effects influence the impact of inherited mutations on offspring behavior.]]>
Thu, 13 Aug 2015 00:00:00 PDT
Consequences of paternally inherited effects on the genetic evaluation of maternal effects. Varona L, Munilla S, Casellas J, Moreno C, Altarriba J
Genet Sel Evol (2015)

Mixed models are commonly used for the estimation of variance components and genetic evaluation of livestock populations. Some evaluation models include two types of additive genetic effects, direct and maternal. Estimates of variance components obtained with models that account for maternal effects have been the subject of a long-standing controversy about strong negative estimates of the covariance between direct and maternal effects. Genomic imprinting is known to be in some cases statistically confounded with maternal effects. In this study, we analysed the consequences of ignoring paternally inherited effects on the partitioning of genetic variance.]]>
Thu, 13 Aug 2015 00:00:00 PDT
Chromatin state analysis of the barley epigenome reveals a higher order structure defined by H3K27me1 and H3K27me3 abundance. Baker K, Dhillon T, Colas I, Cook N, Milne I, Milne L, Bayer M, Flavell AJ
Plant J (Aug 2015)

Combinations of histones carrying different covalent modifications are a major component of epigenetic variation. We have mapped nine modified histones in the barley seedling epigenome by ChIP-seq. The chromosomal distributions of the modifications group them into four different classes and members of a given class also tend to coincide at the local DNA level, suggesting that global distribution patterns reflect local epigenetic environments. We used this peak sharing to define ten chromatin states representing local epigenetic environments in the barley genome. Five states map mainly to genes and five to intergenic regions. Two genic states involving H3K36me3 are preferentially associated with constitutive gene expression, while an H3K27me3-containing genic state is associated with differentially-expressed genes. The ten states display striking distribution patterns that divide barley chromosomes into three distinct global environments. First, telomere-proximal regions contain high densities of H3K27me3 covering both genes and intergenic DNA, together with very low levels of the repressive H3K27me1 modification. Flanking these are gene-rich interior regions that are rich in active chromatin states, greatly decreased levels of H3K27me3 and increasing amounts of H3K27me1 and H3K9me2. Lastly, H3K27me3-depleted pericentromeric regions contain gene islands with active chromatin states separated by extensive retrotransposon-rich regions that are associated with abundant H3K27me1 and H3K9me2 modifications. We propose an epigenomic framework for barley whereby intergenic H3K27me3 specifies facultative heterochromatin in the telomere-proximal regions and H3K27me1 is diagnostic for constitutive heterochromatin elsewhere in the barley genome. This article is protected by copyright. All rights reserved.]]>
Mon, 10 Aug 2015 00:00:00 PDT
BioWardrobe: an integrated platform for analysis of epigenomics and transcriptomics data. Kartashov AV, Barski A
Genome Biol (2015)

High-throughput sequencing has revolutionized biology by enhancing our ability to perform genome-wide studies. However, due to lack of bioinformatics expertise, modern technologies are still beyond the capabilities of many laboratories. Herein, we present the BioWardrobe platform, which allows users to store, visualize and analyze epigenomics and transcriptomics data using a biologist-friendly web interface, without the need for programming expertise. Predefined pipelines allow users to download data, visualize results on a genome browser, calculate RPKMs (reads per kilobase per million) and identify peaks. Advanced capabilities include differential gene expression and binding analysis, and creation of average tag -density profiles and heatmaps. BioWardrobe can be found at http://biowardrobe.com .]]>
Fri, 07 Aug 2015 00:00:00 PDT
The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals. Stel J, Legler J
Endocrinology (Aug 2015)

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.]]>
Tue, 04 Aug 2015 00:00:00 PDT
A GWAS assessment of the contribution of genomic imprinting to the variation of body mass index in mice. Hu Y, Rosa GJ, Gianola D
BMC Genomics (2015)

Genomic imprinting is an epigenetic mechanism that can lead to differential gene expression depending on the parent-of-origin of a received allele. While most studies on imprinting address its underlying molecular mechanisms or attempt at discovering genomic regions that might be subject to imprinting, few have focused on the amount of phenotypic variation contributed by such epigenetic process. In this report, we give a brief review of a one-locus imprinting model in a quantitative genetics framework, and provide a decomposition of the genetic variance according to this model. Analytical deductions from the proposed imprinting model indicated a non-negligible contribution of imprinting to genetic variation of complex traits. Also, we performed a whole-genome scan analysis on mouse body mass index (BMI) aiming at revealing potential consequences when existing imprinting effects are ignored in genetic analysis.]]>
Tue, 04 Aug 2015 00:00:00 PDT
Epigenetic alterations in sperm associated with male infertility. Kitamura A, Miyauchi N, Hamada H, Hiura H, Chiba H, Okae H, Sato A, John RM, Arima T
Congenit Anom (Kyoto) (Aug 2015)

The most common form of male infertility is a low sperm count, known as oligozoospermia. Studies suggest that oligozoospermia is associated with epigenetic alterations. Epigenetic alterations in sperm, which may arise due to the exposure of gametes to environmental factors or those that pre-exist in the sperm of infertile individuals, may contribute to the increased incidence of normally rare imprinting disorders in babies conceived after assisted reproductive technology using the sperm of infertile men. Genomic imprinting is an important developmental process whereby the allelic activity of certain genes is regulated by DNA methylation established during gametogenesis. The aberrant expression of several imprinted genes has been linked to various diseases, malignant tumors, lifestyle and mental disorders in humans. Understanding how infertility and environmental factors such as reproductive toxicants, certain foods, and drug exposures during gametogenesis contribute to the origins of these disorders via defects in sperm is of paramount importance. In this review, we discuss the association of epigenetic alterations with abnormal spermatogenesis and the evidence that epigenetic processes, including those required for genomic imprinting, may be sensitive to environmental exposures during gametogenesis, fertilization and early embryonic development. In addition, we review imprinting diseases and their relationships with environmental factors. While the plasticity of epigenetic marks may make these more susceptible to modification by the environment, this also suggests that aberrant epigenetic marks may be reversible. A greater understanding of this process and the function of epidrugs may lead to the development of new treatment methods for many adult diseases in the future.]]>
Mon, 27 Jul 2015 00:00:00 PDT
Ultrasensitive homogeneous electrochemical strategy for DNA methyltransferase activity assay based on autonomous exonuclease III-assisted isothermal cycling signal amplification. Li W, Liu X, Hou T, Li H, Li F
Biosens Bioelectron (Aug 2015)

DNA methylation catalyzed by methyltransferase (MTase) plays an important role in many biological processes, including gene transcription, genomic imprinting and cellular differentiation. Herein, a simple and novel homogeneous electrochemical strategy for ultrasensitive DNA MTase activity assay has been successfully developed, which is based on methylation-triggered exonuclease (Exo) III-assisted autonomous isothermal cycling signal amplification. A duplex DNA (P1-P2 hybrid) containing the methylation-responsive sequence is ingeniously designed. In the presence of DNA adenine methylation (Dam) methyltransferase (MTase), P1-P2 hybrid is methylated and subsequently recognized and cleaved by Dpn I endonuclease, which triggers the Exo III-catalyzed autonomous cycling cleavage processes. Therefore, a large amount of methylene blue-labeled mononucleotides are released, generating a significantly amplified electrochemical signal toward the Dam MTase activity assay. The directly measured detection limit down to 0.004 U/mL is obtained, which is one or two orders magnitude lower than that of the approaches reported in literature. Since this assay is carried out in homogeneous solution phase under isothermal condition and sophisticated probe immobilization processes are avoided, it is very simple and easy to implement. Due to its advantages of ultrahigh sensitivity, excellent selectivity and simple operation, the as-proposed strategy has great potential in the applications in DNA methylation related clinical practices and biochemical researches.]]>
Sat, 30 May 2015 00:00:00 PDT