Ontology highlight
ABSTRACT:
PROVIDER: PRJNA834094 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19038007_1.fastq.gz | Fastqsanger.gz | |||
| SRR19038007_2.fastq.gz | Fastqsanger.gz | |||
| SRR19038008_1.fastq.gz | Fastqsanger.gz | |||
| SRR19038008_2.fastq.gz | Fastqsanger.gz | |||
| SRR19038009_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Differences in chromatin state inherited from the parental gametes influence the regulation of maternal and paternal alleles in offspring. This phenomenon, known as genomic imprinting, results in genes preferentially transcribed from one parental allele. While local epigenetic factors such as DNA methylation are known to be important for the establishment of imprinted gene expression, less is known about the mechanisms by which differentially methylated regions (DMRs) lead to differences in allelic expression across broad stretches of chromatin. Allele-specific higher-order chromatin structure has been observed at multiple imprinted loci, consistent with the observation of allelic binding of the chromatin-organizing factor CTCF at multiple DMRs. However, whether allelic chromatin structure impacts allelic gene expression is not known for most imprinted loci. Here we characterize the mechanisms underlying brain-specific imprinted expression of the Peg13-Kcnk9 locus, an imprinted region associated with intellectual disability. We performed region capture Hi-C on mouse brain from reciprocal hybrid crosses and found imprinted higher-order chromatin structure caused by the allelic binding of CTCF to the Peg13 DMR. Using an in vitro neuron differentiation system, we show that on the maternal allele, an enhancer-promoter contact formed early in development primes the brain-specific potassium leak channel Kcnk9 for maternal expression prior to neurogenesis. In contrast, this enhancer-promoter contact is blocked by CTCF on the paternal allele, preventing paternal Kcnk9 activation. This work provides a high-resolution map of imprinted chromatin structure and demonstrates that chromatin state established in early development can promote imprinted expression upon differentiation.
2023-08-07 | GSE202251 | GEO
Project description:How constitutive allelic methylation at imprinting control regions (ICRs) interacts with other levels of regulation to drive timely parental allele-specific expression along large imprinted domains remains partially understood at most imprinted loci. To gain insight into the regulation of the Peg13-KcnK9 domain, an imprinted domain with important brain functions, during neural commitment, we performed a detailed integrative analysis of the epigenetic, transcriptomic and cis-spatial organisation in an allele-specific manner in a mouse stem cell-based model of corticogenesis that recapitulates the control of imprinted gene expression in the embryonic brain. We have evidence that despite an allelic higher order chromatin structure associated with the paternally CTCF-bound Peg13 ICR, enhancer-Kcnk9 promoter contacts can occur on both alleles, although they are only productive on the maternal allele. This observation challenges the canonical model in which CTCF binding isolates the enhancer and its target gene on either side, and suggests a more nuanced role for allelic CTCF binding at the ICR of this locus.
2024-02-05 | GSE244145 | GEO
Project description:How constitutive allelic methylation at imprinting control regions (ICRs) interacts with other levels of regulation to drive timely parental allele-specific expression along large imprinted domains remains partially understood at most imprinted loci. To gain insight into the regulation of the Peg13-KcnK9 domain, an imprinted domain with important brain functions, during neural commitment, we performed a detailed integrative analysis of the epigenetic, transcriptomic and cis-spatial organisation in an allele-specific manner in a mouse stem cell-based model of corticogenesis that recapitulates the control of imprinted gene expression in the embryonic brain. We have evidence that despite an allelic higher order chromatin structure associated with the paternally CTCF-bound Peg13 ICR, enhancer-Kcnk9 promoter contacts can occur on both alleles, although they are only productive on the maternal allele. This observation challenges the canonical model in which CTCF binding isolates the enhancer and its target gene on either side, and suggests a more nuanced role for allelic CTCF binding at the ICR of this locus.
2024-02-05 | GSE244144 | GEO
Project description:How constitutive allelic methylation at imprinting control regions (ICRs) interacts with other levels of regulation to drive timely parental allele-specific expression along large imprinted domains remains partially understood at most imprinted loci. To gain insight into the regulation of the Peg13-KcnK9 domain, an imprinted domain with important brain functions, during neural commitment, we performed a detailed integrative analysis of the epigenetic, transcriptomic and cis-spatial organisation in an allele-specific manner in a mouse stem cell-based model of corticogenesis that recapitulates the control of imprinted gene expression in the embryonic brain. We have evidence that despite an allelic higher order chromatin structure associated with the paternally CTCF-bound Peg13 ICR, enhancer-Kcnk9 promoter contacts can occur on both alleles, although they are only productive on the maternal allele. This observation challenges the canonical model in which CTCF binding isolates the enhancer and its target gene on either side, and suggests a more nuanced role for allelic CTCF binding at the ICR of this locus.
2024-02-05 | GSE244146 | GEO
Project description:How constitutive allelic methylation at imprinting control regions (ICRs) interacts with other levels of regulation to drive timely parental allele-specific expression along large imprinted domains remains partially understood at most imprinted loci. To gain insight into the regulation of the Peg13-KcnK9 domain, an imprinted domain with important brain functions, during neural commitment, we performed a detailed integrative analysis of the epigenetic, transcriptomic and cis-spatial organisation in an allele-specific manner in a mouse stem cell-based model of corticogenesis that recapitulates the control of imprinted gene expression in the embryonic brain. We have evidence that despite an allelic higher order chromatin structure associated with the paternally CTCF-bound Peg13 ICR, enhancer-Kcnk9 promoter contacts can occur on both alleles, although they are only productive on the maternal allele. This observation challenges the canonical model in which CTCF binding isolates the enhancer and its target gene on either side, and suggests a more nuanced role for allelic CTCF binding at the ICR of this locus.
2024-02-05 | GSE244143 | GEO
Project description:Although many long non-coding RNAs (lncRNAs) are controlled by genomic imprinting, their roles often remain unknown. The Dlk1-Dio3 imprinted domain expresses the lncRNA Meg3 (also called Gtl2) and multiple microRNAs and snoRNAs from the maternal chromosome. This locus constitutes an epigenetic model for pluripotency and development, particularly for neurogenesis. The domain’s Dlk1 (Delta-like-1) gene encodes a ligand that inhibits Notch1 signalling and regulates diverse developmental processes. Using a hybrid embryonic stem (ES) cell system, we find that Dlk1 becomes imprinted during neural differentiation and that this involves chromatin activation and transcriptional up-regulation on the paternal chromosome. On the maternal chromosome, the Dlk1 gene remains poised. This allelic protection against gene activation is controlled in cis by Meg3 expression and also involves the H3-lysine-27 methyltransferase Ezh2. Maternal Meg3 expression additionally protects against de novo DNA methylation at its promoter. Concordantly, we find that the lncRNA Meg3 is nuclear, accumulates onto the imprinted locus and overlaps in cis with Dlk1 in embryonic cells. Our data evoke an imprinting model in which a mono-allelic lncRNA prevents chromatin and gene activation in cis during development.
2018-04-10 | GSE99903 | GEO
Project description:Inborn defects in DNA repairare associated with complex developmental disorders whose causal mechanisms are poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development. Loss of Ercc1or exposure to mitomycin C triggers the localization of CTCF to heterochromatin, the dissociation of the CTCF-cohesin complex and ATRXfrom promoters and ICRs,altered histone marks and the aberrant developmental expression of imprinted genes without altering DNA methylation. We propose that ERCC1-XPF cooperates with CTCF and the cohesinto facilitatet he developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders.
2017-04-04 | PXD005897 | Pride
Project description:ZFP57 interacts with the germline-derived differentially methylated regions (DMRs) of imprinted genes, and is required to maintain DMR methylation in mouse embryonic stem cells (ESCs). Although DNA methylation has a key role in maintaining genomic imprinting, several imprinted genes are controlled by different mechanisms, and a comprehensive study of the relationship between DMR methylation and imprinted gene expression is lacking. To address this issue, we differentiated wild-type and Zfp57 -/- hybrid mouse ESCs into neural precursor cells (NPCs) and evaluated allelic expression of imprinted genes. In Zfp57-mutant NPCs, we observed loss of allelic bias of all the 35 genes that were imprinted in wild-type cells, demonstrating that Zfp57-dependent methylation is required to globally maintain gene expression imprinting. Analysis of bulk expression showed that most of the genes expressed from the non-methylated chromosome were up-regulated, and most of those expressed from the methylated chromosome were down-regulated in mutant cells, but also that several other imprinted genes acquiring biallelic expression were not significantly affected, suggesting the existence of compensatory mechanisms that control their RNA level. Since neuronal differentiation was impaired in Zfp57-mutant cells, this study also indicates that deregulation of imprinted genes and/or other ZFP57-target non-imprinted genes is incompatible with proper neurogenesis.
2021-07-06 | GSE164669 | GEO
Project description:Mammalian sperm and oocytes have different epigenetic landscapes and are organized in different fashion. Following fertilization, the initially distinct parental epigenomes become largely equalized with the exception of certain loci including imprinting control regions. How parental chromatin becomes equalized and how imprinted genes escape this wave of reprogramming is largely unknown. Here we generated high-resolution maps of parental allele-specific DNase I hypersensitive sites (DHSs) in zygotes and morula embryos by using physically-isolated parental pronuclei, as well as parthenogenetic (PG) and androgenetic (AG) embryos. Allelic transcriptome analyses revealed a high correlation between allelic DHSs and allelic gene expression not only in known imprinted genes but also in dozens of genes not previously known to be imprinted. Interestingly, we found that many paternally- expressed genes harbor paternal allele-specific DHSs (Ps-DHSs) that are highly enriched for histone H3K27 tri-methylation (H3K27me3) but devoid of DNA methylation in maternal allele. Importantly, ectopic removal of the H3K27me3 turns Ps-DHSs into bi- allelic DHSs and induces maternal allele derepression in genes that include maternal DNA methylation-independent imprinted genes Gab1, Sfmbt2, Slc38a4, and Phf17 (also known as Jade1). Thus, our study not only reveals parental allele-specific chromatin accessibility of preimplantation embryos, but also identifies maternal H3K27me3 as a DNA methylation- independent mechanism for genomic imprinting.
2017-07-19 | GSE92605 | GEO
Project description:Biallelic non-productive enhancer-promoter interaction precedes imprinted expression of KcnK9 during mouse neural commitment
| PRJNA1021513 | ENA