Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Non-canonical imprinting ensures embryonic development and restrains placental overgrowth

ABSTRACT: Genomic imprinting regulates parental origin-dependent mono-allelic gene expression. It is mediated by either germline differential methylation of DNA (canonical imprinting) or oocyte-derived H3K27me3 (non-canonical imprinting) in mice. Depletion of Eed, an essential component of Polycomb repressive complex 2, results in genome-wide loss of H3K27me3 in oocytes, which causes loss of non-canonical imprinting (LOI) in embryos. Although Eed maternal KO (matKO) embryos show partial lethality after implantation, it is unknown whether LOI itself contributes to the developmental phenotypes of these embryos, which makes it unclear whether non-canonical imprinting is developmentally relevant. Here, by combinatorial matKO of Xist, a non-canonical imprinted gene whose LOI causes aberrant transient maternal X chromosome inactivation (XCI) at preimplantation, we show that prevention of the transient maternal XCI greatly restores the development of Eed matKO embryos. Moreover, we find that the placentae of Eed matKO embryos are remarkably enlarged in a manner independent of Xist LOI. Heterozygous deletion screening of individual autosomal non-canonical imprinted genes suggests that LOI of the Sfmbt2 miRNA cluster-chromosome 2 miRNA cluster (C2MC), solute carrier family 38 member 4 (Slc38a4), and Gm32885 contributes to the placental enlargement. Taken together, our study provides evidence that Xist imprinting sustains embryonic development and autosomal non-canonical imprinting restrains placental overgrowth.

ORGANISM(S): Mus musculus

PROVIDER: GSE199115 | GEO | 2022/06/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Maternal Eed knockout causes loss of H3K27me3 imprinting and random X-inactivation in the extra-embryonic cells

Project description:Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 lysine 27 tri-methylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we demonstrate that maternal Eed, an essential component of the Polycomb group complex 2 (PRC2), is required for establishing H3K27me3 imprinting. We found that all H3K27me3 imprinted genes, including Xist, lose their imprinted expression in Eed maternal KO (matKO) embryos, resulting in male-biased lethality. Surprisingly, although maternal X chromosome inactivation (XmCI) occurs in Eed matKO embryos at preimplantation due to loss of Xist imprinting, it is resolved at peri-implantation. Ultimately, both X chromosomes are reactivated in the embryonic cell lineage prior to random XCI, and only a single X chromosome undergoes random XCI in the extra-embryonic cell lineage. Thus, our study not only demonstrates an essential role of Eed in H3K27me3 imprinting establishment but also reveals a unique XCI dynamics in the absence of Xist imprinting.

2018-11-26 | GSE116713 | GEO

Genomic imprinting of Xist by maternal H3K27me3

Project description:Maternal imprinting at the Xist gene is essential to achieve paternal allele-specific imprinted X chromosome inactivation (XCI) in female mammals. However, the mechanism underlying the Xist imprinting is unclear. Here we show that the Xist gene is coated with H3K27me3 in mouse oocytes, which persists through preimplantation development. Ectopic removal of H3K27me3 induces maternal Xist expression and maternal XCI, indicating that maternal H3K27me3 is the imprinting mark of Xist.

2017-11-09 | GSE103714 | GEO

Diverse epigenetic mechanisms maintain parental imprints within the embryonic and extraembryonic lineages

Project description:Genomic imprinting and X chromosome inactivation (XCI) require epigenetic mechanisms to direct allele-specific expression. Despite their critical roles in embryonic development, how universal epigenetic regulators coordinate these specific tasks at single loci or across chromosome scales remains understudied. Here, we systematically disrupted essential epigenetic pathways within polymorphic F1 embryos to examine canonical and non-canonical genomic imprinting as well as X chromosome inactivation. We find that DNA methylation and Polycomb group repressors are both indispensable for autosomal imprinting, albeit at distinct gene sets. Moreover, the extraembryonic ectoderm relies on a broader spectrum of imprinting mechanisms, including non-canonical targeting of maternal endogenous retrovirus (ERV) driven promoters by the H3K9 methyltransferase G9a. We further utilize our data to identify Polycomb dependent and independent gene clusters on the imprinted X chromosome, which appears to reflect distinct domains of Xist-mediated suppression. From our data, we assemble a comprehensive inventory of the epigenetic mechanisms utilized in eutherian mammals to maintain parent-specific imprinting, including an expanded view of the placental lineage that comprises multiple unique pathways.

2021-11-12 | GSE171206 | GEO

Switching from Random to Imprinted X-inactivation by Maternal PRC2

Project description:Imprinted X-inactivation is a paradigm of transgenerational epigenetic inheritance in mammals and silences genes exclusively on the paternally-inherited X-chromosome. Here, we test the hypothesis that oocyte-derived maternal Polycomb repressive complex 2 (PRC2) protein EED orchestrates the selective inactivation of the paternal-X in mouse embryos. In maternal Eed null (Eedm-/-) but not zygotic Eed null female and male embryos, the maternal X-chromosome ectopically induced Xist lncRNA, which silences X-linked genes. Subsequently, Xist was silenced from one of the two X-chromosomes in females and from the sole maternal-X in males. As a result, later-stage female Eedm-/- embryos displayed random X-inactivation. The kinetics of Xist RNA induction in Eedm-/- embryos resemble that of early human embryos, which lack oocyte-derived PRC2 and only undergo random X-inactivation. Thus, expression of PRC2 genes in the oocyte and transmission of the gene products to the embryo may dictate the occurrence of imprinted X-inactivation in mammals.

2019-05-02 | GSE123173 | GEO

Allelic histone-to-DNA methylation switch establishes secondary DMR to maintain noncanonical imprinting

Project description:Faithful maintenance of genomic imprinting is essential for mammalian development. While germline DNA methylation-dependent (canonical) imprinting is relatively stable during development, the recently discovered oocyte-derived H3K27me3-mediated noncanonical imprinting is mostly transient in early embryos with only a few genes maintain imprinted expression in the extraembryonic lineage. How these few noncanonical imprinted genes maintain their extraembryonic-specific imprinting is unknown. Here we report that maintenance of extraembryonic-specific noncanonical imprinting requires maternal allele-specific de novo DNA methylation (secondary differentially methylation regions; DMRs) at implantation. The secondary DMRs are located at the gene promoters with paternal allele-specific H3K4me3 preformed during preimplantation development. Importantly, genetic ablation of Eed and DNA methyltransferases revealed that both maternal H3K27me3 and zygotic Dnmt3a/3b are required for establishing secondary DMRs and for maintaining noncanonical imprinting. Thus, our study not only reveals the mechanism underlying maintenance of noncanonical imprinting, but also sheds light on how histone modifications in oocytes and preimplantation embryos may shape the secondary DMRs in post-implantation embryos.

2019-12-26 | GSE130115 | GEO

A bipartite element with allele-specific functions safeguards DNA methylation imprints at the Dlk1-Dio3 locus [4C-seq]

Project description:Dysregulation of imprinted gene loci also referred to as loss of imprinting (LOI) can result in severe developmental defects and other diseases, but the molecular mechanisms that ensure imprint stability remain incompletely understood. Here, we dissect the functional components of the imprinting control region of the essential Dlk1-Dio3 locus (called IG-DMR) and the mechanism by which they ensure imprinting maintenance. Using pluripotent stem cells carrying an allele-specific reporter system, we demonstrate that the IG-DMR consists of two antagonistic regulatory elements: a paternally methylated CpG-island that prevents the activity of Tet dioxygenases and a maternally unmethylated regulatory element, which serves as a non-canonical enhancer and maintains expression of the maternal Gtl2 lncRNA by precluding de novo DNA methyltransferase function. Targeted genetic or epigenetic editing of these elements leads to LOI with either bi-paternal or bi-maternal expression patterns and respective allelic changes in DNA methylation and 3D chromatin topology of the entire Dlk1-Dio3 locus. Although the targeted repression of either IG-DMR or Gtl2 promoter is sufficient to cause LOI, the stability of LOI phenotype depends on the IG-DMR status, suggesting a functional hierarchy. These findings establish the IG-DMR as a novel type of bipartite control element and provide mechanistic insights into the control of Dlk1-Dio3 imprinting by allele-specific restriction of the active DNA (de)methylation machinery.

2021-09-14 | GSE148315 | GEO

Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues [RNA-Seq]

Project description:Background: Genomic imprinting is an epigenetic phenomenon that allows a subset of genes to be expressed mono-allelically based on parent-of-origin, and is typically regulated by differential DNA methylation inherited from gametes. Imprinting is pervasive in murine extra-embryonic lineages and, uniquely, the imprinting of several genes has been found to be conferred non-canonically through maternally-inherited repressive histone modification H3K27me3. However, the underlying regulatory mechanisms of non-canonical imprinting in post-implantation development remain unexplored. Results: We identify imprinted regions in post-implantation epiblast and extra-embryonic ectoderm (ExE) by assaying allelic histone modifications (H3K4me3, H3K36me3, H3K27me3), gene expression and DNA methylation in reciprocal C57BL/6 and CAST hybrid embryos. We distinguish loci with DNA methylation- dependent (canonical) and independent (non-canonical) imprinting by assaying hybrid embryos with ablated maternally-inherited DNA methylation. We find that non-canonical imprints are localized to endogenous retrovirus-K (ERVK) long terminal repeats (LTRs), which act as imprinted promoters specifically in extra-embryonic lineages. Transcribed ERVK LTRs are CpG-rich and located in close proximity to gene promoters, and imprinting status is determined by their epigenetic patterning in the oocyte. Finally, we show that oocyte-derived H3K27me3 associates with non-canonical imprints is not maintained beyond pre-implantation development, and is replaced by secondary imprinted DNA methylation on the maternal allele in post-implantation ExE, while being completely silenced by bi-allelic DNA methylation in epiblast. Conclusions: This study reveals distinct epigenetic mechanisms regulating non-canonical imprinted gene expression between embryonic and extra-embryonic development, and identifies an integral role for ERVK LTR repetitive elements.

2019-09-19 | GSE124215 | GEO

Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues [Bisulfite-Seq]

2019-09-19 | GSE124213 | GEO

Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues [ChIP-Seq]

2019-09-19 | GSE124212 | GEO

Placental Transcriptome and Stunting

Project description:<p>Therian mammals and angiosperms evolved genomic imprinting in nutritive tissues, the placenta and endosperm, where maternal and paternal genomes are in conflict with respect to resource allocation. In imprinted genes, transcription is repressed from either the paternal or the maternal allele, resulting in allele specific expression (ASE). We studied variation in ASE of imprinted genes in human placentas to detect loss of imprinting (LOI), which refers to departures from mono-allelic expression. The placental tissue was collected in connection with a multigenerational, prospective cohort study in Mali, West Africa, in which individuals were followed from infancy and early childhood to adulthood (age 18+ years). When young women for whom we had longitudinal growth data gave birth, we collected placental tissue and umbilical cord tissue. We genotyped the umbilical cord tissue and saliva samples from parents using targeted DNAseq to identify SNPs in 96 genes known from the literature to be imprinted in human placentas. We used RNAseq to analyze allele specific expression of the heterozygous SNPs. Our results provide the first systematic analysis of variation in LOI across genes and individuals and make it possible to test the hypothesis that modulation of imprinting is an epigenetic mechanism that contributes to the regulation of offspring growth. </p>

| phs001782 | dbGaP

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data