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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE254806 | GEO | 2024/03/24

REPOSITORIES: GEO

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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 (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.

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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).

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Therapeutic effect of γ-secretase inhibition in KrasG12V-driven non-small cell lung carcinoma through derepression of DUSP1 phosphatase and inhibition of ERK

Project description:We have investigated the role of the Notch pathway in the generation and maintenance of KrasG12V-driven non-small cell lung carcinomas (NSCLCs). We demonstrate by genetic means that γ-secretase and Rbpj activities are both essential in the formation of NSCLCs. Interestingly, pharmacologic treatment of mice carrying endogenous NSCLCs with a γ-secretase inhibitor (GSI) blocks cancer growth and induces partial regression. Treated cancers show a reduction in Hes1 levels, reduced phosphorylated Erk, decreased proliferation and higher apoptosis. We demonstrate that HES1 directly binds and represses the promoter of DUSP1, a dual phosphatase with activity against phospho-ERK, and this repression is relieved by GSI treatment both in mouse and human NSCLCs. Our data provide proof for the in vivo therapeutic potential of γ-secretase inhibitors in primary NSCLCs and provide a mechanistic explanation for its therapeutical effect. We have included 6 samples. 3 with vehicle and 3 with the gamma-secretase inhibitor DAPT and we compare both groups.

2012-12-01 | E-GEOD-38054 | biostudies-arrayexpress

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

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

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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.

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Differential Notch target genes expression profile upon GSI washout.

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Differential gene expression of a gamma secretase inhibitor treated human oral squamous cell carcinoma cell line

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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 (ChIP-Seq).

Project description: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).

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Identification of naturally short gamma-secretase substrates

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