RNAseq of Notch signaling responsive and unresponsive thymus DN1a/b cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE128926 | GEO | 2019/09/01
REPOSITORIES: GEO
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Project description:We report the gene expression profile of single cell BM LMPPs that are either responsive to Notch signals, or unresponsive to Notch signals due to absence of expression of RBPJ, a key mediator of the Notch signaling pathway.
2019-09-01 | GSE128963 | GEO
Project description:We report the gene expression profile of recent thymic emigrant (RTE) that are either responsive to Notch signals, or unresponsive to Notch signals during their maturation process. Notch responsiveness is controled by the expression of RBPJ, a key mediator of the Notch signaling pathway.
2023-04-12 | GSE229284 | GEO
Project description:We report the gene expression profile of recent thymic emigrant (RTE) that are either responsive to Notch signals, or unresponsive to Notch signals during their maturation process. Notch responsiveness is controled by the expression of RBPJ, a key mediator of the Notch signaling pathway.
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Project description:RNAseq of Notch signaling responsive and unresponsive thymus DN1a/b cells
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Project description:Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. At the molecular level, the key components of the Notch pathway are the NOTCH-family receptors, the ligands of the DSL (Delta, Serrate, Lag-2) family and the transcription factor CSL [CBF1/RBPJ, Su(H), Lag-1]. Upon ligand binding, the NOTCH Intra-Cellular Domain (NOTCH ICD) translocates into the nucleus and forms a complex with RBPJ to activate the transcription of target genes. In the absence of NOTCH ICD, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 as a novel interactor of RBPJ. We discovered that L3MBTL3 competes with NOTCH ICD for binding to RBPJ. In the absence of NOTCH ICD, RBPJ recruits L3MBTL3 and its co-factor KDM1A [lysine (K)-specific demethylase 1A] to the promoters/enhancers of Notch target genes to promote H3K4me2 demethylation and transcriptional repression. In three distinct cell contexts in which Notch signaling governs cell fate, i.e., mature T-cells as well as brain and breast tumor cells, the loss of L3MBTL3 results in the de-repression of Notch target genes. Finally, the genetic analyses of the homologs of RBPJ and L3MBTL3 in Drosophila melanogaster and Caenorhabditis elegans demonstrate that the functional link between RBPJ/Su(H)/lag-1 and L3MBTL3/dL(3)mbt/lin-61 is evolutionarily conserved, thus identifying L3MBTL3 as a universal modulator of Notch signaling in metazoans.
2017-10-17 | PXD004196 | Pride
Project description:Dysregulation of the Notch-RBPJ signaling pathway has been found associated with various human diseases including cancers; however, precisely how this key signaling pathway is fine-tuned via its interactors and modifications is still largely unknown. In this study, using a proteomic approach, we identified FBXO42 as a novel RBPJ interactor. FBXO42 promotes RBPJ polyubiquitination on lysine (K) 175 via K63 linkage, which enhances the association of RBPJ with chromatin remodeling complexes and induces a global chromatin relaxation. Genetically depleting FBXO42 or pharmacologically targeting its E3 ligase activity attenuates the Notch signaling-related leukemia development in vivo. Taken together, our findings not only revealed FBXO42 as a critical regulator of the Notch pathway by modulating RBPJ-dependent global chromatin landscape changes, but also provide insights into the therapeutic intervention of the Notch pathway for leukemia treatment.
2022-10-13 | PXD034938 | Pride
Project description:scRNAseq of Notch signaling responsive and unresponsive bone marrow lymphoid-primed multipotent progenitors (BM LMPPs)
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Project description:The NOTCH signaling pathway plays an important role in regulating various biological processes, including cell proliferation, lineage specification and apoptosis. Multiple components of the NOTCH pathway have been identified in mammalian preimplantation embryos. However, the precise role of NOTCH pathway in early embryonic development is poorly understood, especially in domestic animals. Here, we show that key transcripts of the NOTCH pathway exhibit a dynamic pattern throughout early embryonic development with an abundant level before embryonic genome activation in cattle. We also confirmed the presence of active NOTCH1 and RBPJ. By using pharmacological and RNAi tools, we demonstrated that the NOTCH pathway is required for the proper development of bovine early embryos. This functional consequence could be partly attributed to the major transcriptional mediator-RBPJ, whose deficiency also compromised the embryo quality. Indeed, we observed a significant increase of histone H3 serine 10 phosphorylation (pH3S10, a mitosis marker) positive blastomeres in not only NOTCH1 depleted embryos but RBPJ depleted ones. Importantly, RNA-seq analysis revealed that either NOTCH1 or RBPJ depletion triggers a reduction in H1FOO that encodes the oocyte-specific linker histone H1 variant. Interestingly, depleting H1FOO also results in detrimental effects on the developmental competence of early embryos, similar with NOTCH1 inhibition. Overall, our results reveal a crucial role for NOTCH pathway in regulating bovine preimplantation development, likely by controlling cell proliferation and maintaining H1FOO expression.
2021-01-31 | GSE158679 | GEO
Project description:Notch signalling plays crucial roles in mediating cell fate choices in all metazoans largely by specifying the transcriptional output of one cell in response to a neighbouring cell. The DNA-binding protein RBPJ is the principle effector of this pathway in mammals and together with the transcription factor moiety of Notch (NICD) it regulates the expression of target genes. The prevalent view presumes that RBPJ statically occupies consensus binding sites while exchanging repressors for activators in response to NICD. We present the first specific RBPJ chromatin immunoprecipitation and high-throughput sequencing study in mammalian cells. To dissect the mode of transcriptional regulation by RBPJ and identify its direct targets, whole genome binding profiles were generated for RBPJ, its coactivator p300, NICD and the histone H3 modifications H3K4me3, H3K4me1 and H3K27ac in myogenic cells under active or inhibitory Notch signalling conditions. Our results demonstrate dynamic binding of RBPJ in response to Notch activation at essentially all sites co-occupied by NICD. Additionally, we identify a distinct set of sites where RBPJ recruits neither NICD nor p300, and binds DNA statically, irrespective of Notch activity. These findings significantly modify our views on how RBPJ and Notch signalling mediate their activities and consequently impact on cell fate decisions. ChIP (chromatin immunoprecipitation) is followed by deep sequencing to generate genome-wide patterns of RBP-J binding in mouse C2C12 cells under various conditions. Cells were either Notch activated by exposure to immobilized ligand or by overexpression of NICDGFP, or Notch inhibited by treatment with DAPT. Notch activation and inhibition treatments were applied for 6h and 24h. In addition to RBP-J, p300 and NICDGFP were profiled by ChIP-Seq and gene expression was assessed by RNA-Seq.
2013-05-13 | E-GEOD-37184 | biostudies-arrayexpress
Project description:Notch signalling plays crucial roles in mediating cell fate choices in all metazoans largely by specifying the transcriptional output of one cell in response to a neighbouring cell. The DNA-binding protein RBPJ is the principle effector of this pathway in mammals and together with the transcription factor moiety of Notch (NICD) it regulates the expression of target genes. The prevalent view presumes that RBPJ statically occupies consensus binding sites while exchanging repressors for activators in response to NICD. We present the first specific RBPJ chromatin immunoprecipitation and high-throughput sequencing study in mammalian cells. To dissect the mode of transcriptional regulation by RBPJ and identify its direct targets, whole genome binding profiles were generated for RBPJ, its coactivator p300, NICD and the histone H3 modifications H3K4me3, H3K4me1 and H3K27ac in myogenic cells under active or inhibitory Notch signalling conditions. Our results demonstrate dynamic binding of RBPJ in response to Notch activation at essentially all sites co-occupied by NICD. Additionally, we identify a distinct set of sites where RBPJ recruits neither NICD nor p300, and binds DNA statically, irrespective of Notch activity. These findings significantly modify our views on how RBPJ and Notch signalling mediate their activities and consequently impact on cell fate decisions.
2013-05-13 | GSE37184 | GEO