Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA342629 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4238030_1.fastq.gz | Fastqsanger.gz | |||
| SRR4238030_2.fastq.gz | Fastqsanger.gz | |||
| SRR4238025_1.fastq.gz | Fastqsanger.gz | |||
| SRR4238025_2.fastq.gz | Fastqsanger.gz | |||
| SRR4238026_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Nono, a novel bivalent domain factor, regulates Erk signaling and mouse embryonic stem cell pluripotency
| PRJNA342617 | ENA
Project description:Nono, a novel bivalent domain factor, regulates Erk signaling and mouse embryonic stem cell pluripotency [ChIP-Seq]
| PRJNA296947 | ENA
Project description:Here we report that Nono instead functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We demonstrate that Nono loss leads to robust self-renewing mESCs with enhanced expression of Nanog and Klf4, epigenome and transcriptome re-patterning to a “ground-like state” with global reduction of H3K27me3 and DNA methylation resembling the Erk inhibitor PD03 treated mESCs and 2i (both GSK and Erk kinase inhibitors)-induced “ground state”. Mechanistically, Nono and Erk co-bind at a subset of development-related, bivalent genes. Ablation of Nono compromises Erk activation and RNA polymerase II C-terminal Domain serine 5 phosphorylation, and while inactivation of Erk evicts Nono from chromatin, revealing reciprocal regulation. Furthermore, Nono loss results in a compromised activation of its target bivalent genes upon differentiation and the differentiation itself. These findings reveal an unanticipated role of Nono in collaborating with Erk signaling to regulate the integrity of bivalent domain and mESC pluripotency.
2016-10-18 | GSE86817 | GEO
Project description:Here we report that NONO, a nuclear para-speckle component, instead functions as a chromatin regulator in mESCs acting in the ERK signaling pathway to regulate the balance between ground state versus mESCs primed for differentiation. NONO loss increases a \u201cground-like\u201d population of mESCs favoring self-renewal and more resist to differentiation, partially mimicking the effects of 2i. Mechanistically, NONO and ERK mainly co-binds a subset of development related, bivalent genes. Importantly, NONO and ERK reciprocally regulate one another, i.e. NONO regulates ERK activation while ERK controls NONO chromatin association, forming a self-reinforcing feedback loop. Our findings thus reveal a cell intrinsic mechanism involving NONO and ERK, which impact the balance between self-renewal and differentiation, respectively.
2016-10-18 | GSE73426 | GEO
Project description:The objective of this study was to identify genes regulated by canonical Wnt signaling in mouse embryonic stem cells (ESCs).Canonical Wnt signaling supports the pluripotency of mouse ESCs but also promotes differentiation of early mammalian cell lineages. To explain these paradoxical observations, we explored the gene regulatory networks at play. Canonical Wnt signaling is intertwined with the pluripotency network comprising Nanog, Oct4, and Sox2 in mouse ESCs. In defined media supporting the derivation and propagation of mouse ESCs, Tcf3 and ?-catenin interact with Oct4; Tcf3 binds to Sox motif within Oct-Sox composite motifs that are also bound by Oct4-Sox2 complexes. Further, canonical Wnt signaling up-regulates the activity of the Pou5f1 distal enhancer via the Sox motif in mouse ESCs. When viewed in the context of published studies on Tcf3 and ?-catenin mutants, our findings suggest that Tcf3 counters pluripotency by competition with Sox2 at these sites, and Tcf3 inhibition is blocked by ?-catenin entry into this complex. Wnt pathway stimulation also triggers ?-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs. The failure to activate these targets in the presence of a MEK/ERK inhibitor essential for mouse ESC culture suggests that MEK/ERK signaling and canonical Wnt signaling combine to promote mouse ESC differentiation. Triplicates of mouse embryonic stem cells cultured with GSK3 inhibitor CHIR99021 or with Wnt pathway inhibitor XAV939.
2013-03-01 | E-GEOD-43420 | biostudies-arrayexpress
Project description:The objective of this study was to investigate the roles of GSK3 inhibitor CHIR99021 and MEK inhibitor PD0325901 on 2i-adapted mouse embryonic stem cells (ESCs) in serum-free conditions.Canonical Wnt signaling supports the pluripotency of mouse ESCs but also promotes differentiation of early mammalian cell lineages. To explain these paradoxical observations, we explored the gene regulatory networks at play. Canonical Wnt signaling is intertwined with the pluripotency network comprising Nanog, Oct4, and Sox2 in mouse ESCs. In defined media supporting the derivation and propagation of mouse ESCs, Tcf3 and β-catenin interact with Oct4; Tcf3 binds to Sox motif within Oct-Sox composite motifs that are also bound by Oct4-Sox2 complexes. Further, canonical Wnt signaling up-regulates the activity of the Pou5f1 distal enhancer via the Sox motif in mouse ESCs. When viewed in the context of published studies on Tcf3 and β-catenin mutants, our findings suggest that Tcf3 counters pluripotency by competition with Sox2 at these sites, and Tcf3 inhibition is blocked by β-catenin entry into this complex. Wnt pathway stimulation also triggers β-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs. The failure to activate these targets in the presence of a MEK/ERK inhibitor essential for mouse ESC culture suggests that MEK/ERK signaling and canonical Wnt signaling combine to mouse promote ESC differentiation. Triplicates of mouse embryonic stem cells cultured under the following conditions: 1) CHIR99021+PD0325901+LIF; 2) CHIR99021+PD0325901; 3) CHIR99021; 4) PD0325901; 5) DMSO
2013-03-01 | E-GEOD-43421 | biostudies-arrayexpress
Project description:The objective of this study was to identify the direct target genes of M-NM-2-catenin acting downstream of canonical Wnt signaling in mouse embryonic stem cells (ESCs).Canonical Wnt signaling supports the pluripotency of mouse ESCs but also promotes differentiation of early mammalian cell lineages. To explain these paradoxical observations, we explored the gene regulatory networks at play. Canonical Wnt signaling is intertwined with the pluripotency network comprising Nanog, Oct4, and Sox2 in mouse ESCs. In defined media supporting the derivation and propagation of mouse ESCs, Tcf3 and M-NM-2-catenin interact with Oct4; Tcf3 binds to Sox motif within Oct-Sox composite motifs that are also bound by Oct4-Sox2 complexes. Further, canonical Wnt signaling up-regulates the activity of the Pou5f1 distal enhancer via the Sox motif in mouse ESCs. When viewed in the context of published studies on Tcf3 and M-NM-2-catenin mutants, our findings suggest that Tcf3 counters pluripotency by competition with Sox2 at these sites, and Tcf3 inhibition is blocked by M-NM-2-catenin entry into this complex. Wnt pathway stimulation also triggers M-NM-2-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs. The failure to activate these targets in the presence of a MEK/ERK inhibitor essential for mouse ESC culture suggests that MEK/ERK signaling and canonical Wnt signaling combine to promote mouse ESC differentiation. bCatenin ChIP-seq using anti-FLAG antibody and Streptavidin were otained from embryonic stem cells treated by CHIR99021 for 24 hours. Input without IP process were used as the control.
2013-03-01 | E-GEOD-43565 | biostudies-arrayexpress
Project description:We identified non-POU domain-containing octamer-binding protein (NONO), a Drosophila behavior human splicing (DBHS) protein, among the most upregulated mRNA splicing factors in glioblastoma multiforme (GBM). NONO was associated with poor prognosis in GBM patients, and overexpression of NONO promoted GBM cell proliferation, invasion and tumorigenesis in a GBM orthotopic xenograft model. Through RNA sequencing based transcriptomic profiling, we found that knockdown of NONO resulted in global changes in alternative splicing-intron retention, and identified GPX1 and CCN1 as two pre-mRNAs targeted by NONO. NONO directly bound to the intron of GPX1 pre-mRNA through the RNA-recognition motifs 2 (RRM2) domain and required interaction with another DBHS protein family member, PSPC1. Knockdown of NONO interfered with redox homeostasis in cells, at least partially, through abnormal splicing of GPX1. Finally, Auranofin, a small-molecule inhibitor targeting NONO, inhibited GBM growth in an orthotopic xenograft model in mice. Taken together, our data revealed that NONO was a key regulator of mRNA splicing in GBM, and that targeting NONO represents a novel and effective therapeutic strategy for the treatment of GBM.
2022-08-03 | GSE191021 | GEO
Project description:We identified non-POU domain-containing octamer-binding protein (NONO), a Drosophila behavior human splicing (DBHS) protein, among the most upregulated mRNA splicing factors in glioblastoma multiforme (GBM). NONO was associated with poor prognosis in GBM patients, and overexpression of NONO promoted GBM cell proliferation, invasion and tumorigenesis in a GBM orthotopic xenograft model. Through RNA sequencing based transcriptomic profiling, we found that knockdown of NONO resulted in global changes in alternative splicing-intron retention, and identified GPX1 and CCN1 as two pre-mRNAs targeted by NONO. NONO directly bound to the intron of GPX1 pre-mRNA through the RNA-recognition motifs 2 (RRM2) domain and required interaction with another DBHS protein family member, PSPC1. Knockdown of NONO interfered with redox homeostasis in cells, at least partially, through abnormal splicing of GPX1. Finally, Auranofin, a small-molecule inhibitor targeting NONO, inhibited GBM growth in an orthotopic xenograft model in mice. Taken together, our data revealed that NONO was a key regulator of mRNA splicing in GBM, and that targeting NONO represents a novel and effective therapeutic strategy for the treatment of GBM.
2022-08-03 | GSE190950 | GEO
Project description:In this study, we provide evidence to show that the expression of PRC2-recruting factor Jarid2 is largely reduced in both naïve mESC and Erk1/Erk2 double knockout (Erk1/2-dKO) mESCs, which can be rescued by reactivation of FGF/MARK signaling in naïve mESCs or ectopic Erk1 expression in Erk1/2-dKO mESCs, suggesting the FGF/ERK signaling positively regulates the Jarid2 expression in mESCs. Consistent with the Jarid2 function in the PRC2 recruitment, the global Ezh2 occupancy and histone H3K27me3 are largely reduced at CpG islands (CGIs) and bivalent promoters in both naïve mESCs and Erk1/Erk2-dKO mESCs, which can be fully restored by ectopic expression of Jarid2 expression, suggesting the reduced Jarid2-mediated PRC2 recruitment is a main molecular mechanism leading to the global reduction of PRC2 occupancy at CpG islands and bivalent promoters in naïve mESCs. At the transcriptional level, although both PRC2 occupancy and histone H3K27me3 modification are reduced at bivalent promoters, there exist two groups of genes with distinct expression status. the FGF/ERK signaling target genes are silenced while the Wnt signaling target genes are largely de-repressed, which is caused by the chemical activation of Wnt/beta-catenin signaling in naïve mESCs. Further ChIP-seq analyses demonstrate an increased occupancy of β-catenin at its activated gene promoters in naïve mESCs. These results suggest the transcriptional activation of bivalent genes in naïve mESCs is predominantly determined by the presence of transcriptional factors but not the status of PRC2 occupancy at gene promoters.
2020-10-13 | GSE157748 | GEO