Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA205241 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tissue-specific pioneer factors associate with androgen receptor cistromes and transcription programs. [ChIP-Seq]
| PRJNA205243 | ENA
Project description:Androgen receptor (AR) is a hormonal transcription factor (TF) that binds to cis-regulatory elements of prostate lineage-specific genes to govern androgen response and progression of prostate cancer (PCa). This AR cistrome has been reported to be controlled by multiple chromatin-pioneering factors such as FOXA1, HOXB13, and GATA2. However, how these pioneer factors cooperate to regulate the AR cistrome remains unclear. Here, through comparative ChIP-seq analyses, we found that FOXA1 alone was sufficient to recruit AR to its binding sites regardless of H3K4me1. FOXA1 further enlisted HOXB13 and/or GATA2 to augment AR binding and enhancer activation, while HOXB13 and/or GATA2 alone were unable to recruit each other, nor AR. Moreover, HOXB13 knockdown attenuated AR and GATA2 expression and chromatin binding but failed to reprogram their cistromes, suggesting a role as a cofactor rather than a pioneer factor.
2026-03-04 | GSE296178 | GEO
Project description:We report the in vivo androgen receptor (AR) binding sites in murine prostate, epididymis and kidney in response to physiological androgen testosterone using ChIP-sequencing and gene expression profiling by microarray. From AR cistrome analysis, we identified tissue-specific collaborating factors i.e. FoxA1 in prostate, Hnf4a in kidney and AP2a in epididymis and validated by ChIP-seq. The ChIP experiments have been performed using antibodies specific to AR, FoxA1, Hnf4a, AP-2a and IgG non-specific antibody as a negative control. Examination of AR binding sites in murine androgen-responsive tissues prostate, epididymis and kidney using ChIP-seq. Further analysis of AR cistromes led to identification of tissue-specific collaborating factors and these collaborating factors are validated by ChIP-seq from the same tissues. Two parallel IgG samples were sequenced, merged together and used as a control data set. Parallel ChIP-seq samples were sequenced and merged for each replicate wherever required to contain approximately the same amount of reads across all tissues and conditions. All ChIP-seq experiments are performed in biological duplicates except for the castrated conditions.
2014-01-21 | E-GEOD-47192 | biostudies-arrayexpress
Project description:Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of cancer death worldwide. Emerging evidence suggests that the androgen receptor (AR) is involved in ESCC tumorigenesis. However, how AR exerts its genomic functions in ESCC remains unknown. Here, by defining AR cistromes and analyzing androgen-regulated transcriptomes, we find that AR downregulates the majority of its target genes in ESCC cells. We further find that the pioneer factor GATA3 governs AR-repressed transcription by recruiting SMRT/HDAC3 co-repressors to target gene loci. Importantly, genetic inhibition of GATA3 or pharmacological inhibition of AR/HDAC3 relieves AR-mediated gene repression, leading to ESCC cell growth inhibition in vitro and in vivo. Our findings reveal molecular mechanisms underlying the oncogenomic function of AR in ESCC and identify the GATA3-directed AR transcriptional repression program as a therapeutic target for ESCC.
2020-10-21 | GSE142556 | GEO
Project description:Pioneer factors control transcription by opening chromatin, but a lack of chemical tools has made it difficult to study pioneer activity with kinetic precision. We recently reported covalent chemical probes that remodel the genomic localization of FOXA1, a prototypical pioneer factor essential for the growth of many breast and prostate cancers. Here, we expand the chemical toolbox for FOXA1 by developing a dTAG-based system for small molecule-induced FOXA1 degradation. Coupling pharmacological perturbations to rapid measurements of chromatin structure and function, we find that FOXA1 exclusively initiates chromatin opening at its genomic binding sites, but, interestingly, this unidirectional outcome both activates and represses gene transcription depending on the chromatin environment surrounding FOXA1-binding sites. These effects apply to both androgen receptor (AR) target genes and other FOXA1 targets. Our findings thus uncover regulatory features that translate FOXA1 pioneering activity into both activation and repression of transcriptional programs critical for cancer growth.
2026-02-25 | GSE315959 | GEO
Project description:Activation of the androgen receptor (AR) is the key lineage-specific oncogenic pathway and the primary therapeutic target in prostate cancer. While AR signaling is enabled by the pioneer transcription factor FOXA1, its homolog FOXA2 is specifically expressed in advanced lineage plasticity prostate cancers that have lost the AR signaling axis. However, their roles and utility as drug targets remain incompletely characterized. Here, we show an unexpected collaboration of FOXA1 and FOXA2 in mediating AR-independent cell proliferation in different lineage plasticity cancer subtypes. Conversely, joint loss-of-function or pharmacologic disruption of FOXA1 and FOXA2 leads to the collapse of lineage-specific oncogenic transcription factors followed by cell cycle arrest. In summary, our findings uncover a druggable dependency for AR-positive and -negative prostate cancers.
2026-01-27 | PXD057803 | Pride
Project description:Despite recent advances in the treatment of pancreatic adenocarcinoma (PDAC), clinical outcome remains poor. Previous evidence linked the pioneer transcription factor FOXA1 as a mediator of new regulatory elements that drive tumour progression in models of late-stage disease. Given the critical role of FOXA1 as a pioneer factor for nuclear receptor (NR) transcription factors (TF) in breast and prostate cancer (Estrogen Receptor and Androgen Receptor), we hypothesised that FOXA1 might function with a NR in PDAC (1) (2). Using RIME, our unbiased approach for discovering endogenous protein complexes, we identified HNF4A and HNF4G as reproducible, FOXA1-associated proteins, a finding that was validated in clinical samples of PDAC. Using complex and diverse PDAC models, we show that gene transcription in the classical subtype of pancreatic cancer is regulated by FOXA1/GATA5/6 and HNF4G. We show that HNF4G drives primary disease, in part by recruiting the methyltransferase PRMT1 to regulatory regions. In primary tumour context, HNF4G is the dominant protein and the presence of HNF4G masks FOXA1 activity, resulting in FOXA1 being present, but functionally redundant in primary disease. During transition to metastasis however, HNF4G expression decreases, which unmasks FOXA1 activity, where it becomes transcriptionally active and a subsequent driver of metastasis. We provide new molecular insight into the key TFs in PDAC and the stage-specific activity of these proteins.
2025-08-13 | PXD045980 | Pride
Project description:The nucleosome is a fundamental unit of chromatin in eukaryotes, and generally prevents the binding of transcription factors to genomic DNA. Pioneer transcription factors overcome the nucleosome barrier, and bind their target DNA sequences in chromatin. OCT4 is a representative pioneer transcription factor that plays a role in stem cell pluripotency. In the present study, we biochemically analyzed the nucleosome binding by OCT4. Crosslinking mass spectrometry showed that OCT4 binds the nucleosome.
| PXD019160 | JPOST Repository
Project description:Androgen receptor (AR) drives prostate cancer (CaP) even after androgen deprivation therapy (ADT) failed. Inhibiting AR’s transcription factor function to overcome acquired resistance to ADT is an attractive therapeutic avenue. However, which AR-coregulator interaction should be targeted is not clear, AR-coregulator complex higher order structures and stoichiometry are unknown, and how manipulating AR-coregulator interactions impacts the AR cistrome is not understood. Here, we examine interactions between AR and WD repeat 77 (WDR77, non-catalytic component of the methylosome complex), which are enriched in ADT-resistant CaP and mediate CaP cell survival. We performed CUT&RUN assays defined AR and WDR77 cistromes, the WDR77-dependence of the AR cistrome and the overlap between the AR and WDR77 cistromes in CaP cells.
2025-01-10 | GSE252993 | GEO