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Identification of Fra-1/AP-1 binding sites in macrophages

ABSTRACT: Identification of Fra-1/AP-1 binding sites in macrophages

PROVIDER: PRJNA741256 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14907706.fastq.gz	Fastqsanger.gz
	SRR14907707.fastq.gz	Fastqsanger.gz
	SRR14907708.fastq.gz	Fastqsanger.gz
	SRR14907709.fastq.gz	Fastqsanger.gz
	SRR14907710.fastq.gz	Fastqsanger.gz

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Identification of Fra-1/AP-1 binding sites in macrophages

Project description:The polarization and activation of macrophages are controlled synergistically by transcription factors such as NF-κB and AP-1 transcription factor members. Surprisingly, little is known about the role of the AP-1 member, Fra-1, during macrophage responses. To determine the full spectrum of Fra-1 binding sites in macrophages, chromatin immunoprecipitation sequencing analysis was performed in macrophages pooling down for the transcription factor Fra-1.

2021-06-25 | GSE178865 | GEO

Transcript profiling in peritoneal macrophages from wildtype, Fra-1ΔMxCre or Fra-2ΔLysMCre mice

Project description:The polarization and activation of macrophages are controlled synergistically by transcription factors such as NF-κB and AP-1 transcription factor members. Surprisingly, little is known about the role of the Fra proteins, both members of the AP-1 transcription factor family, in macrophage activity. To determine the full profile of Fra network, microarray RNA expression analysis using Agilent Technologies platform was performed in wild-type, Fra-1ΔMxCre or Fra-2ΔLysMCre macrophages.

2021-05-17 | GSE128787 | 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

2019-09-01 | GSE132098 | GEO

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.

2022-04-21 | GSE149621 | GEO

Genome-wide maps of apurinic sites (AP-sites) and 8-oxoG derived secondary AP-sites

Project description:Genome-wide maps of apurinic sites (AP-sites) and 8-oxoG derived secondary AP-sites

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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

Endogenous interaction profiling identifies DDX5 as an oncogenic coactivator of transcription factor Fra-1 [RNA-seq]

Project description:Fra-1, a member of the activator protein 1 (AP-1) family, is overexpressed in triple-negative breast cancer (TNBC) and plays crucial roles in tumor progression. However, a systematic analysis of the composition of the Fra-1 protein network specifically on chromatin is still missing. Here we performed endogenous purification of Fra-1 transcriptional complex under ChIP conditions, followed by mass spectrometry, to identify chromatin-bound partners of Fra-1 in TNBC cells. This study allowed the identification of 118 interactors, highlighting DDX5 as the high ranking of Fra-1 interacting proteins. DDX5, a previously unrecognized protein in the network, is recruited globally to Fra-1 binding sites and shares a substantial set of Fra-1 target genes required for the TNBC cell growth. We provide evidence that DDX5 expression enhances Fra-1 transcriptional activity, thereby enhancing Fra-1-driven tumorigenesis. By integrating ChIP-seq and RNA-seq, we show that DDX5 target gene signature predicts poor clinical outcome in breast cancer patients. DDX5 protein level was higher in triple-negative basal like tumors than in non-basal like tumors, including luminal A, luminal B and HER2-enriched subtypes. Collectively, this comprehensive Fra-1 interaction profiling provides a broad and deep view of Fra-1 chromatin interaction landscape, which will help in deciphering mechanisms of AP-1 regulation of gene expression.

2019-09-03 | GSE112962 | GEO

Endogenous interaction profiling identifies DDX5 as an oncogenic coactivator of transcription factor Fra-1 [ChIP-seq]

2019-09-03 | GSE112961 | GEO

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

| PRJNA545944 | ENA

Expression data of A549 Fra-2 overexpressing cells

Project description:Fra-2 belongs to the activated protein-1 (AP-1) family and is involved in the mechanisms of resistance to platinum in ovarian cancer and to anti-EGFR therapy in NSCLC. We used microarrays to identify genes potentially regulated by Fra-2 transciptional activity.

2022-09-23 | GSE213816 | GEO

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