Profiling of differential allelic expression in mouse placenta from reciprocal crosses
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE29690 | GEO | 2011/06/15
SECONDARY ACCESSION(S): PRJNA141109
REPOSITORIES: GEO
Similar Datasets
Project description:Many questions about the regulation, functional specialization, computational prediction, and evolution of genomic imprinting would be better addressed by having an exhaustive genome-wide catalog of genes that display parent-of-origin differential expression. As a first-pass scan for novel imprinted genes, we performed mRNA-seq experiments on E17.5 mouse placenta cDNA samples from reciprocal cross F1 progeny of AKR and PWD mouse strains, and quantified the allele-specific expression and the degree of parent-of-origin effect transcriptome-wide. We confirmed the imprinting status of 23 known imprinted genes in the placenta, and found that 12 genes reported previously to be imprinted in other tissues are also imprinted in mouse placenta. Through a well-replicated design using an orthogonal technology, we verified five novel imprinted genes that are not known to be imprinted in mouse. It appears that most of the strongly imprinted genes have already been identified, at least in the placenta, and that evidence supports perhaps 100 additional weakly imprinted genes. Despite previous appearance that the placenta tends to display an excess of maternally-expressed imprinted genes, when the full set of genes is uniformly scored as in this study, this maternal bias disappeared. Examine allelic expression in E17.5 placenta tissues from two individual samples, one from each of the two reciprocal crosses.
2011-06-15 | E-GEOD-29690 | biostudies-arrayexpress
Project description:The discovery of genomic imprinting through studies of manipulated mouse embryos indicated that the paternal genome has a major influence on placental development. However, previous research has not demonstrated paternal bias in imprinted genes. We applied RNA sequencing to trophoblast tissue from reciprocal hybrids of horse and donkey, where genotypic differences allowed parent-of-origin identification of most expressed genes. Using this approach, we identified a core group of 15 ancient imprinted genes of which 10 were paternally expressed. An additional 78 candidate novel imprinted genes identified by RNA-seq also showed paternal bias. Pyrosequencing was used to confirm the imprinting status of six of the novel genes, including the insulin receptor (INSR), which may play a role in growth regulation with its reciprocally imprinted ligand, histone acetyltransferase (HAT1), the first example of an imprinted gene involved in chromatin modification, and LY6G6C, the first imprinted gene to be identified in the major histocompatibility complex. The 78 novel candidate imprinted genes displayed parent-of-origin expression bias in placenta but not fetus, and most showed less than 100% silencing of the imprinted allele. Some displayed variability in imprinting status among individuals. This results in a unique epigenetic signature for each placenta that contributes to variation in the intrauterine environment and thus presents the opportunity for natural selection to operate on parent-of-origin differential regulation. Taken together, these features highlight the plasticity of imprinting in mammals and the central importance of the placenta as a target tissue for genomic imprinting. Examine allelic expression from four individual samples of invasive trophoblast tissue of the chorionic girdle from gestation day 33 conceptuses of horse, donkey, mule and hinny.
2013-05-24 | E-GEOD-30243 | biostudies-arrayexpress
Project description:The discovery of genomic imprinting through studies of manipulated mouse embryos indicated that the paternal genome has a major influence on placental development. However, previous research has not demonstrated paternal bias in imprinted genes. We applied RNA sequencing to trophoblast tissue from reciprocal hybrids of horse and donkey, where genotypic differences allowed parent-of-origin identification of most expressed genes. Using this approach, we identified a core group of 15 ancient imprinted genes of which 10 were paternally expressed. An additional 78 candidate novel imprinted genes identified by RNA-seq also showed paternal bias. Pyrosequencing was used to confirm the imprinting status of six of the novel genes, including the insulin receptor (INSR), which may play a role in growth regulation with its reciprocally imprinted ligand, histone acetyltransferase (HAT1), the first example of an imprinted gene involved in chromatin modification, and LY6G6C, the first imprinted gene to be identified in the major histocompatibility complex. The 78 novel candidate imprinted genes displayed parent-of-origin expression bias in placenta but not fetus, and most showed less than 100% silencing of the imprinted allele. Some displayed variability in imprinting status among individuals. This results in a unique epigenetic signature for each placenta that contributes to variation in the intrauterine environment and thus presents the opportunity for natural selection to operate on parent-of-origin differential regulation. Taken together, these features highlight the plasticity of imprinting in mammals and the central importance of the placenta as a target tissue for genomic imprinting.
2013-05-24 | GSE30243 | GEO
Project description:Genomic imprinting is an epigenetic phenomenon by which certain genes display differential expression in a parent-of-origin-dependent manner. Hundreds of imprinted genes have been identified from several plant species. Here we identified, with a high level of confidence, 208 imprinted candidates from rice. Imprinted genes of rice showed limited association to the transposable elements, which contrasts with findings from Arabidopsis. Generally, imprinting in rice is conserved within species, but intraspecific variation was detected as well.
2018-05-15 | GSE113769 | GEO
Project description:The maternal and paternal copies of the genome are both required for mammalian development and this is primarily due to imprinted genes, those that are mono-allelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilisation. There are a large number of germline DMRs that have not yet been associated with imprinting and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs, specifically in the human placenta, and investigated the dynamics of imprinted DMRs during development in somatic and extra-embryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 116 human tissue samples, publically available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. 43 known and 101 novel imprinted DMRs were identified in the human placenta, by comparing methylation between diandric and digynic triploids and female and male gametes. 72 novel DMRs showed a pattern consistent with placental-specific imprinting and this monoallelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation specifically in placenta. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation.
2015-12-23 | GSE76273 | GEO
Project description:The maternal and paternal copies of the genome are both required for mammalian development and this is primarily due to imprinted genes, those that are mono-allelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilisation. There are a large number of germline DMRs that have not yet been associated with imprinting and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs, specifically in the human placenta, and investigated the dynamics of imprinted DMRs during development in somatic and extra-embryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 116 human tissue samples, publically available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. 43 known and 101 novel imprinted DMRs were identified in the human placenta, by comparing methylation between diandric and digynic triploids and female and male gametes. 72 novel DMRs showed a pattern consistent with placental-specific imprinting and this mono-allelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation specifically in placenta. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation
2015-12-22 | GSE74738 | GEO
Project description:Hybrid phenotypes that contribute to postzygotic reproductive isolation often exhibit pronounced asymmetry, both between reciprocal crosses and between the sexes in accordance with Haldane's rule. Inviability in mammalian hybrids is associated with parent-of-origin placental growth abnormalities for which misregulation of imprinted genes is the leading candidate mechanism. However, direct evidence for the involvement of imprinted genes in hybrid growth dysplasia is limited. We used transcriptome and reduced representation bisulfite sequencing to conduct the first genome-scale assessment of the contribution of imprinted genes to parent-of-origin placental growth dysplasia in the cross between the house mouse (Mus musculus domesticus) and the Algerian mouse (Mus spretus). Imprinted genes with transgressive expression and methylation were concentrated in the Kcnq1 cluster, which contains causal genes for prenatal growth abnormalities in mice and humans. Hypermethylation of the cluster’s imprinting control region, and consequent misexpression of the genes Phlda2 and Ascl2, is a strong candidate mechanism for transgressive placental undergrowth. Transgressive placental and gene regulatory phenotypes, including expression and methylation in the Kcnq1 cluster, were more extreme in hybrid males. While consistent with Haldane’s rule, male-biased defects are unexpected in rodent placenta because the X-chromosome is effectively hemizygous in both sexes. In search of an explanation we found evidence of leaky imprinted (paternal) X-chromosome inactivation in hybrid female placenta, an epigenetic disturbance that may buffer females from the effects of X-linked incompatibilities to which males are fully exposed. Sex differences in chromatin structure on the X and sex-biased maternal effects are non-mutually exclusive alternative explanations for adherence to Haldane’s rule in hybrid placenta. The results of this study contribute to understanding the genetic basis of hybrid inviability in mammals, and the role of imprinted genes in speciation.
2020-11-09 | GSE161051 | GEO
Project description:Mammalian parental imprinting represents an exquisite form of epigenetic control regulating the parent-specific monoallelic expression of genes in clusters. While imprinting perturbations are widely associated with developmental abnormalities, the intricate regional interplay between imprinted genes makes interpreting the contribution of gene dosage effects to phenotypes a challenging task. Using mouse models with distinct deletions in an intergenic region controlling imprinting across the Dlk1-Dio3 domain, we link changes in genetic and epigenetic states to allelic-expression and phenotypic outcome in vivo. This determined how hierarchical interactions between regulatory elements orchestrate robust parent-specific expression, with implications for non-imprinted gene regulation. Strikingly, flipping imprinting on the parental chromosomes by crossing genotypes of complete and partial intergenic element deletions, rescues the lethality of each deletion on its own. Our work indicates that parental origin of an epigenetic state is irrelevant as long as appropriate balanced gene expression is established and maintained at imprinted loci.
2022-07-09 | GSE207600 | GEO
Project description:Genomic imprinting is a mechanism in which the expression of genes varies depending on their parent-of-origin. Imprinting occurs through differential DNA methylation and histone modifications on the two parental alleles, with most imprinted genes marked by CpG-rich differentially methylated regions (DMRs). DNA methylation profiling in cases of uniparental disomy (UPD) provides a unique system permitting the study of DNA derived from a single parent (PMID: 20631049). Approximately 70 human imprinted genes have been described, and imprinted loci have been associated with diseases such as diabetes and cancer. We profiled parent of origin DNA methylation marks to find novel imprinted loci. Methods: We have an unprecedented collection of whole blood DNA from XX patients with UPD covering 18 different chromosomes, allowing for the efficient detection of DMRs associated with imprinted genes for 84% of the human genome. Our study is complimented with Ovarian Teratoma DNA (maternal DNA) and Complete hydatidiform Mole (paternal DNA). DNA methylation was profiled using Illumina Infinium 450K Methylation BeadArrays. Imprinted DMRs were defined by sites at which the maternal and paternal methylation levels diverged significantly from the biparental average. We confirmed novel DMRs by bisulfite sequencing of informative trios and SequenomEpiTYPER assays. Allelic specific gene expression studies were also performed by RNA sequencing in independent biparental controls. Findings: Our results provide for the first comprehensive map of the human imprintome, doubling the number of known imprinted regions. We identified a total of 71 DMRs, 41 of which were novel. 27 novel DMRs were maternally methylated and 14 were paternally methylated. We identified DMRs on chromosomes 5, 21 and 22 previously considered devoid of imprinting, highlighting potential parent-of-origin effects in chromosomal aneuploidies such as Down syndrome. We also found DMRs in genes associated with Schizophrenia and epilepsy. Interpretation: Our data provide the first comprehensive genome-wide map of imprinted sites in the human genome, and provide novel insights into potential parent-of-origin effects in human disorders. 66 UPD samples analyzed in total, From each individual, whole bllod DNA was extracted and global DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.
2016-06-01 | E-GEOD-64244 | biostudies-arrayexpress
Project description:Genomic imprinting describes the expression of a subset of mammalian genes from one parental chromosome. The parent-of-origin specific expression of imprinted genes relies on DNA methylation of CpG-dinucleotides at differentially methylated regions (DMRs) during gametogenesis. We identified the paternally methylated DMRs at mouse chromosome 1 near the imprinted Zdbf2 gene using a methylated-DNA immunoprecipitation-on-chip (meDIP-on-chip) method applied to DNA from parthenogenetic (PG)- and androgenetic (AG)-derived cells and sperm.
2010-05-05 | GSE18126 | GEO