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Series GSE232552 Query DataSets for GSE232552
Status Public on Apr 22, 2024
Title FOXA2/AP-1 drives prostate cancer lineage plasticity [ChIP-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary FOXA (Forkhead Box Protein A) family proteins function as pioneer transcription factors by loosening the compact chromatin structure and facilitating access for other transcription factors. The role of FOXA1 has been intensively studied in normal prostate epithelial cells and the adenocarcinoma subtype of prostate cancer (PCa) where it acts as a critical pioneer factor for the chromatin binding of androgen receptor (AR). Recent studies have indicated the emergence of FOXA2 as an adaptive response to AR signaling inhibition, particularly in prostate tumors that have undergone lineage reprogramming to a neuroendocrine PCa subtype. However, the molecular basis for this transition from FOXA1 to FOXA2 and its role in regulating the development of PCa lineage plasticity remains unclear. In this study, we show that FOXA2 binds to distinct chromatin regions in multiple AR-null PCa models with different molecular subtypes and that its binding is dependent on an epigenetic factor, LSD1. More importantly, we demonstrate that FOXA2 can function as a major pioneer factor of JUN and govern the chromatin binding of AP-1 complex in PCa exhibiting lineage plasticity. Mechanistically, differential reprogramming of JUN activates lineage-specific super-enhancers that may promote PCa progression by enhancing cell state transitions to multiple lineages. Overall, our study reveals a pivotal function of the LSD1-FOXA2 axis in rewiring AP-1 to induce differential transcriptional reprogramming required for PCa lineage plasticity.
 
Overall design ChIP-seq analysis of H3K27Ac in PC3 cells. ChIP-seq analysis of FOXA2, JUN, and FOSL1 in PC3 cells treated with siFOXA2 versus siNTC. ChIP-seq analysis of FOXA2 treated with vehicle versus LSD1 inhibitor (ORY-1001, C12) in PC3cells. ChIP-seq analyses of H3K4me2 in NCI-H660 cells. ChIP-seq analyses of FOXA2 in NCI-H660 cells with vehicle versus LSD1 inhibitor (ORY-1001). ChIP-seq analyses of JUN in NCI-H660 cells treated with siFOXA2 versus siNTC. ATAC analysis in PC3 and NCI-H660 cells. ChIP-seq analyses of FOXA2, JUN in LNCaP cells stably expressing FOXA2. ChIP-seq analysis of FOXA2 treated with vehicle versus LSD1 inhibitor (ORY-1001) in DKO cells.
 
Contributor(s) Wang Z, Cai C
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Submission date May 15, 2023
Last update date Apr 22, 2024
Contact name Zifeng Wang
E-mail(s) wzifeng8@gmail.com
Phone 6174709887
Organization name UMASS Boston
Department CPCT
Lab Changmeng Cai
Street address 100 Morrissey Blvd, ISC/4610
City Boston
State/province Massachusetts
ZIP/Postal code 02125
Country USA
 
Platforms (3)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL30172 NextSeq 2000 (Mus musculus)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (24)
GSM7350172 NCI-H660 cells, ORY-1001, ChIP-FOXA2
GSM7350173 NCI-H660 cells, vehicle, ChIP-FOXA2
GSM7350174 NCI-H660 cells, siFOXA2, ChIP-JUN
This SubSeries is part of SuperSeries:
GSE232555 FOXA2/AP-1 drives prostate cancer lineage plasticity
Relations
BioProject PRJNA972717

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Supplementary file Size Download File type/resource
GSE232552_RAW.tar 4.5 Gb (http)(custom) TAR (of BED, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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