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Differential Notch target genes expression profile upon GSI washout.

ABSTRACT: The Notch signaling pathway regulates several processes including development and differentiation and its aberrant regulation leads to several diseases. Here, we analyzed the gene expression profile upon washout of the Notch inhibitor DAPT in mouse pre-T (Beko) cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE235982 | GEO | 2024/03/24

REPOSITORIES: GEO

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Differential Notch target genes expression profile upon HDAC3 loss-of-function.

Project description:The Notch signaling pathway regulates several differentiation and developmental processes in both pre- and post-natal life and its aberrant regulation leads to diseases, including cancer. Here, we investigated the role of histone deacetylase 3 (HDAC3) on the regulation of the Notch-dependent gene expression program in mouse pre-T (Beko) cells. We first defined Notch target genes as those genes that are downregulated upon inhibition of the Notch pathway using DAPT, a gamma-secretase inhibitor (GSI). Subsequently, we investigated the role of HDAC3 in the regulation of Notch target genes by shRNA- and pharmacologically (apicidin)-mediated loss-of-function of HDAC3.

2020-02-04 | GSE106361 | GEO

Differential genome-wide profile of histone modifications upon treatment with gamma-secretase inibithor (GSI) DAPT [ChIP-seq]

Project description:The Notch signaling pathway regulates several processes including development and differentiation and its aberrant regulation leads to several diseases. Here, we investigated the differential chromatin accessibility, genome-wide distribution of the transcription factor RBPJ and the differential regulation of H3K4me1 and H3K4me3 upon pharmacological inhibition of the Notch pathway with gamma-secretase inibibitor (GSI) DAPT in mouse pre-T (Beko) cells.

2024-03-24 | GSE254806 | GEO

Differential genome-wide profile of RBPJ, H3K4me1 and H3K4me3 as well as differential chromatin accessibility upon treatment with gamma-secretase inibithor (GSI) DAPT (ChIP-Seq).

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Differential genome-wide profile of RBPJ, H3K4me1 and H3K4me3 as well as differential chromatin accessibility upon treatment with gamma-secretase inibithor (GSI) DAPT (ATAC-Seq).

2024-03-24 | GSE235977 | GEO

Response of C2C12-hN1∆ECD to DAPT washout

Project description:C2C12 cells expressing constitutively active hN1∆ECD were activated by complete DAPT washout for 1h or 6h, or left in 10 uM DAPT

2016-09-04 | GSE72847 | GEO

Response of C2C12-hN1âECD to DAPT washout

Project description:C2C12 cells expressing constitutively active hN1âECD were activated by complete DAPT washout for 1h or 6h, or left in 10 uM DAPT 2 Samples and 1 Control

2016-09-04 | E-GEOD-72847 | biostudies-arrayexpress

Site-specific methylation of Notch1 controls the amplitude and duration of the Notch1 response

Project description:Physiologically, Notch signal transduction plays a pivotal role in differentiation; pathologically, Notch signaling contributes to the development of cancer. Transcriptional activation of Notch target genes involves cleavage of the Notch receptor in response to ligand binding, production of the Notch intracellular domain (NICD), and NICD migration into the nucleus and assembly of a coactivator complex. Posttranslational modifications of the NICD are important for its transcriptional activity and protein turnover. Deregulation of Notch signaling and stabilizing mutations of Notch1 have been linked to leukemia development. We found that the methyltransferase CARM1 (coactivator-associated arginine methyltransferase 1; also known as PRMT4) methylated NICD at five conserved arginine residues within the C-terminal transactivation domain. CARM1 physically and functionally interacted with the NICD-coactivator complex and was found at gene enhancers in a Notch-dependent manner. Although a methylation-defective NICD mutant was biochemically more stable, this mutant was biologically less active as measured with Notch assays in embryos of Xenopus laevis and Danio rerio. Mathematical modeling indicated that full but short and transient Notch signaling required methylation of NICD. Analysis of gene expression upon inactivation and activation of Notch signaling in Beko cells. Beko cells were treated with DAPT or DMSO for 24h. Or Beko cells were infected with a DNMAML-ER or Notch1-ER fusion protein. After Selection cells were treated with 4-OHT (Tamoxifen) or Ethanol for 48h.

2015-03-26 | E-GEOD-62528 | biostudies-arrayexpress

Transcriptomic analysis of chic embryos forebrain lacking Notch signalling

Project description:The generation of diverse neuronal types and subtypes from multipotent progenitors during development is crucial for assembling functional neural circuits in the adult central nervous system. It is well known that Notch signalling pathway through the inhibition of proneural genes is a key regulator of neurogenesis in the vertebrate central nervous system. However, its role during hypothalamus formation along with its downstream effectors remains poorly defined. Here, we have transiently blocked Notch activity in chick embryos and used global gene expression analysis to provide evidence that Notch signalling modulates the generation of neurons in the early developing hypothalamus by lateral inhibition. Most importantly, we have taken advantage of this model to identify novel targets of Notch signalling, such as Tagln3 and Chga, which were expressed in hypothalamic neuronal nuclei. This data gives essential advances into the early generation of neurons in the hypothalamus. We demonstrate that inhibition of Notch signalling during early development of the hypothalamus enhances expression of several new markers. These genes must be considered as important new targets of the Notch/proneural network. Four sets of samples were used for analysing transcriptome changes in DAPT treated chicl embryos. The rostral part of the head (including the anterior forebrain, optic vesicles and overlying tissue) was collected from control embryos and DAPT-treated embryos at stage HH13.

2013-12-10 | E-GEOD-53129 | biostudies-arrayexpress

Genome-wide profile of RBPJ and differential H3K27ac profile upon treatment with HDAC-inhibitor apicidin.

Project description:The Notch signaling pathway regulates several differentiation and developmental processes in both pre- and post-natal life and its aberrant regulation leads to diseases, including cancer. Here, we investigated the genome-wide distribution of the transcription factor RBPJ and the differential regulation of H3K27ac upon pharmacological inhibition of histone deacetylase 3 (HDAC3) with apicidin in mouse pre-T (Beko) cells.

2020-02-04 | GSE119797 | GEO

Differential gene regulation in DAPT-treated Hydra reveals candidate direct Notch signalling targets

Project description:In Hydra, Notch inhibition causes defects in head patterning and prevents differentiation of proliferating nematocyte progenitor cells into mature nematocytes. To understand the molecular mechanisms by which the Notch pathway regulates these processes, we performed RNA-seq and identified genes that are differentially regulated in response to 48 h of treating the animals with the Notch inhibitor DAPT. To identify candidate direct regulators of Notch signalling, we profiled gene expression changes that occur during subsequent restoration of Notch activity and performed promoter analyses to identify RBPJ transcription factor-binding sites in the regulatory regions of Notch-responsive genes. Interrogating the available single-cell sequencing data set revealed the gene expression patterns of Notch-regulated Hydra genes. Through these analyses, a comprehensive picture of the molecular pathways regulated by Notch signalling in head patterning and in interstitial cell differentiation in Hydra emerged. As prime candidates for direct Notch target genes, in addition to Hydra (Hy)Hes, we suggest Sp5 and HyAlx. They rapidly recovered their expression levels after DAPT removal and possess Notch-responsive RBPJ transcription factorbinding sites in their regulatory regions

2021-09-27 | GSE184492 | GEO

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