Identification of maternal imprinting control regions (ICRs) in the post-implantation mouse embryo.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE32687 | GEO | 2012/10/04
SECONDARY ACCESSION(S): PRJNA146899
REPOSITORIES: GEO
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Project description:Genomewide DNA methylation profiles, generated by MeDIP-seq, for 8.5dpc wildtype and Dnmt3l-/+ mouse embryos were compared to identify differentially methylated regions (DMRs) that depend on the activity of the de novo DNA methyltransferase cofactor Dnmt3l in the oocyte. These DMRs were further characterised by their methylation state in mature mouse sperm and in the livers of inter-subspecies newborn mice. Maternal ICRs were identified by hypomethylation in Dnmt3l-/+ embryos as well as sperm, and maternal allele-specific methylation in liver. MeDIP-seq for two pools of wildtype and two pools of Dnmt3l-/+ mouse 8.5dpc embryos, the sperm of three sires, and 12 pools of three different embryonic livers each. Sliding window read count comparison between wildtype and Dnmt3l-/+ embryos, and between wildtype embryos and sperm samples. Read count comparison between the parental alleles at known SNP sites in inter-subspecies liver data.
2012-10-04 | E-GEOD-32687 | biostudies-arrayexpress
Project description:During oogenesis, DNA methyltransferase 3-like (Dnmt3l) is required for the establishment of the maternal germline DNA methylation imprints that in the offspring, govern the parent-of-origin-specific expression of most known imprinted genes (Science 2001, 294:2536-9). Dnmt3l-deficient dams were crossed with wildtype sires to obtain Dnmt3l-/+ embryos that lack maternal methylation imprints. Gene expression was measured in Dnmt3l-/+ and wildtype embryos and is expected to differ for imprinted genes that are under the control of a maternal methylation mark. Experiment Overall Design: 1 normal control sample/array. 2 biologically replicate Dnmt3l-/+ samples/arrays.
2008-06-16 | E-GEOD-8756 | biostudies-arrayexpress
Project description:During oogenesis, DNA methyltransferase 3-like (Dnmt3l) is required for the establishment of the maternal germline DNA methylation imprints that in the offspring, govern the parent-of-origin-specific expression of most known imprinted genes (Science 2001, 294:2536-9). Dnmt3l-deficient dams were crossed with wildtype sires to obtain Dnmt3l-/+ embryos that lack maternal methylation imprints. Gene expression was measured in Dnmt3l-/+ and wildtype embryos and is expected to differ for imprinted genes that are under the control of a maternal methylation mark. Keywords: genetic modification, DNA methylation
2008-04-14 | GSE8756 | GEO
Project description:In mammals, chromatin marks at imprinted genes are asymmetrically inherited from each parent to control gene expression. Many genomic imprints are determined by differentially methylated regions (DMRs), but these have not been comprehensively mapped physically or functionally in mouse preimplantation embryos. To address this, we measured genome-wide DNA methylation in individual haploid uniparental parthenogenetic haploid (ph) and androgenetic haploid (ah) E3.5 blastocysts by micro-whole-genome bisulfite sequencing (µWGBS). For comparison, we also included ahESC and phESC lines in the analysis.Comparison of DNA methylomes from uniparental blastocysts with those of control blastocysts (produced by intracytoplasmic sperm injection) identified 859 DMRs. Haploid ES cells showed overall erosion of those DMRs, in contrast to diploid ES cells that relatively maintained differential methylation.
2021-03-02 | GSE152105 | GEO
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
Project description:We present genome-scale maps of DNA methylation in early human development and perform comparative analysis to mouse that confirm a conserved global erasure of the paternal genome. We find that while many global features of the early embryo are consistent between the two species, the target sequences in which DNA methylation is maintained are distinct. Repetitive elements show a broader range of class specific behaviors in the human embryo and a larger degree of methylation escape in human sperm. We identify thousands of differentially methylated regions (DMRs) that are likely of maternal origin and found that these gamete contributed DMRs are far more species-specific than expected given the conservation of canonical imprint control regions (ICRs). Finally, we extended our studies to the derivation of new human embryonic stem cell (ESC) lines and found notable divergences in DNA methylation signatures from those found in the human embryo and different mouse ESC derivation conditions. Comparison of DNA methylation patterns in human early development, human ESC derivation and mouse ESC derivation
2014-07-23 | E-GEOD-51239 | biostudies-arrayexpress
Project description:DNA methylation is essential for embryonic development and implicated in the regulation of genomic imprinting. Genomic imprinting is established in the germline through parent-specific methylation of distinct cis-regulatory DNA sequences, called imprinting control regions (ICRs). Which factors bind to the opposing chromatin states at ICRs within the same nuclear environment was not systematically addressed. By using a proximity labelling approach with the methylation sensitive transcription factor ZFP57, we identified ATF7IP and other major components of the epigenetic maintenance machinery at ICRs.
2023-03-10 | PXD034918 | Pride
Project description:We did RNA-seq analysis to compare gene expression profiles in mouse embryos with or without ZFP57. We also perfromed whole-genome bisulfite sequencing analysis (WGBS) for the Zfp57 mutant mouse embryos and control heterozygous embryos. We analyzed DNA methylation at the imprinting control regions (ICRs), differentially methylation regions (DMRs) and repetitive elements including LINE-1, LINE-2, SINE, LTR and IAP.
2021-01-27 | GSE165079 | GEO
Project description:Genomic imprinting is an allele-specific gene expression system important for mammalian development and function. The molecular basis of genomic imprinting is allele-specific DNA methylation 2. While it is well known that the de novo DNA methyltransferases Dnmt3a/b are responsible for the establishment of genomic imprinting, how the methylation mark is erased during primordial germ cell (PGC) reprogramming remains a mystery. Here we report that Tet1 plays a critical role in the erasure of genomic imprinting. We show that despite their identical genotype, progenies derived from mating between Tet1-KO males and wild-type females exhibit a number of variable phenotypes including placental, fetal and postnatal growth defects, and early embryonic lethality. These defects are, at least in part, caused by the dysregulation of imprinted genes, such as Peg10 and Peg3, which exhibit aberrant hypermethylation in the paternal allele of differential methylated regions (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next generation due to paternal functional loss of Tet1. Genome-wide DNA methylation analysis of E13.5 PGCs and sperm derived from Tet1-KO mice reveals hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to PGCs. Dynamics of methylation change in Tet1-affected sites suggested that Tet1 swipes remaining methylation including imprinted genes at late reprogramming stage. We also revealed that Tet1play a role in paternal imprinting erasure in females germline. Thus, our study establishes a critical function for Tet1 in the erasure of genomic imprinting. Gene expression analysis of E9.5 embryos
2013-12-02 | E-GEOD-49761 | biostudies-arrayexpress
Project description:Genomic imprinting is regulated by parental-specific epigenetic marks that differentiate between maternal and paternal chromosomes. Despite identical DNA sequence, the presence or absence of DNA methylation leads to the establishment of two distinct epigenetic states at Imprinting Control Regions (ICR). Here we combine targeted epigenome engineering to generate ectopic loci in the mouse embryonic stem cell genome that recapitulate the epigenetic properties of ICRs. We describe these ectopic ICRs as strong cis-regulatory sequences that can adopt and memorise one of two opposing epigenetic states, dependent of pre-imposed DNA methylation. This bistability is unique to ICRs and enabled us to systematically study the genetic and epigenetic determinants required for creating and maintaining the observed states. Through sequence manipulation we show that the ICR DNA sequence confers autonomy of ICRs and is required for creating epigenetic bistability. Genetic screens using DNA-methylation-sensitive reporters identify key components involved in regulating maintenance of epigenetic states. Besides DNMT1, UHRF1 and ZFP57, we identify novel factors that prevent switching between methylated and unmethylated states and validate two of these candidates, ATF7IP and ZMYM2, to be important for epigenetic memory at ICRs. In summary we show that the DNA sequence of ICRs provides the prerequisite for establishment of two distinct epigenetic states, while DNA and histone modifications ensure their stable propagation.
2022-07-20 | GSE203404 | GEO