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Transcriptional down-regulation of the TGFB2 gene by multiple Fra-1-bound enhancers showing different molecular and functional features in a Triple Negative Cancer (ATAC-Seq)

ABSTRACT: mapping of chromatin accessibility in MDA-MB-231 cells in presence and absence of Fra-1 by ATAC-seq experiments

ORGANISM(S): Homo sapiens

PROVIDER: GSE208441 | GEO | 2023/07/25

REPOSITORIES: GEO

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Transcriptional down-regulation of the TGFB2 gene by multiple Fra-1-bound enhancers showing different molecular and functional features in a Triple Negative Cancer (ChIP-Seq)

Project description:genome-wide mapping of H3K36me3 histone mark in the MDA-MB-231 cell line

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Identification of Fra-1 and/or Fra-2 regulated genes in MDA-MB231 cells

Project description:In the paper "Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers" by Bejjani et al., we identified Fra-1 and/or Fra-2 target genes in MDA-MB-231 cells. si RNA against Fra-1 and against Fra-2 were transfected in MDA-MB-231 cells either independenlty or simultaneously to identify genes regulated specifically by Fra-1 or Fra-2 and genes regulated redundantly or complementarily by Fra-1 and Fra-2 total RNA were purified and biotinylated sense-strand cDNA were produced. cDNA targets were used to probe Affymetrix GeneChip Human Gene 2.0 ST arrays

2021-02-23 | GSE146823 | GEO

genome-wide mapping of Fra-1 and Fra-2 binding sites in MDA-MB-231 cell line

Project description:we report the mapping of Fra-1 and Fra-2 binding site on MDA-MB-231 cell line genome

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Mapping of p300/CBP binding sites in MDA-MB-231 cells transfected with a control siRNA or a siRNA directed against Fra-1(FOSL1)

Project description:In the article "Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers" by Bejjani et al., we mapped p300/CBP binding sites in MDA-MB-231 cells transfected with a control siRNA or a siRNA directed against Fra-1(FOSL1) to study whether Fra-1 can modulate p300/CBP recruitment on MDA-MB-231 genome

2021-02-23 | GSE163304 | GEO

Transcriptional down-regulation of the TGFB2 gene by multiple Fra-1-bound enhancers showing different molecular and functional features in a Triple Negative Cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-07-25 | GSE208443 | GEO

NG-Capture C analysis of 35 gene loci regulated by Fra-1 in MDA-MB-231 cells

Project description:In the article "Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers" by Bejjani et al., we used NG Capture-C approach to identify regulatory elements interacting with the promoters of 35 Fra-1 regulated genes in the triple negative breast cancer cell line MDA-MB-231

2021-02-23 | GSE146824 | GEO

Transcriptional down-regulation of the TGFB2 gene by multiple Fra-1-bound enhancers showing different molecular and functional features in a Triple Negative Cancer

Project description:Transcriptional down-regulation of the TGFB2 gene by multiple Fra-1-bound enhancers showing different molecular and functional features in a Triple Negative Cancer

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Blocking Fra-1 sensitizes triple-negative breast cancer to olaparib

Project description:Fra-1 (FOSL1) is overexpressed in triple-negative breast cancer (TNBC). Fra-1 is a member of the activator protein 1 (AP-1) transcription factor complex, which plays crucial roles in tumor progression and treatment resistance. We have previously identified 118 proteins that interact with endogenous chromatin-bound Fra-1 in TNBC cells in a large screen, and these included PARP1(Poly (ADP-ribose) polymerase 1). PARP1 inhibitor olaparib is currently in clinical use for treatment of BRCA-mutated TNBC breast cancer. Here, we demonstrate that this interaction impacts the efficacy of olaparib treatment. We corroborate that PARP1 interacts with Fra-1, and we show that PARP1 downregulates Fra-1 and consequently reduces AP-1 transcriptional activity. Inhibition of PARP1, on the other hand, increases Fra-1 levels and enhances its transcriptional activity, which in turn can increase treatment resistance. However, by inhibiting Fra-1, we found that TNBC cells became sensitized to olaparib treatment. We compared Fra-1 chromatin binding sites with the Fra-1 and PARP1 regulated transcriptomes, and found that a large fraction of PARP1-regulated genes was dependent on Fra-1. We further show that PARP1 protein levels significantly correlate with Fra-1 in clinical breast cancer tumors, and we identify that high PARP1 expression is indicative of a poor clinical outcome in breast cancer patients overall, but not in basal-like tumors. In conclusion, by exploring the functionality of the Fra-1 and PARP1 interaction, we propose that targeting Fra-1 could serve as a therapeutic approach to improve olaparib treatment outcome for TNBC patients.

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genome-wide mapping of Fra-1 and Fra-2 binding sites in MDA-MB-231 cell line

Project description:genome-wide mapping of Fra-1 and Fra-2 binding sites in MDA-MB-231 cell line

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