GEO series
FOXA2/AP-1 drives prostate cancer lineage plasticity [ChIP-seq]
GSE232552
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
24 samples
Submitted 2024/04/22
Platform GPL30173Platform GPL18573Platform GPL30172
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.
Published in
Wang Z, Townley SL, Zhang S et al.
· Nature communications 2024
· PMID 38851846
· doi:10.1038/s41467-024-49234-9
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE232552_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 24 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA972717 and SRA study SRP437782. Searching any of these in the dataset finder brings you back here.
Study design
24 conditions, each sampled once — no replicated groups
Read from 24 sample titles: 24 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM7350172 NCI-H660 cells, ORY-1001, ChIP-FOXA2
- GSM7350173 NCI-H660 cells, vehicle, ChIP-FOXA2
- GSM7350174 NCI-H660 cells, siFOXA2, ChIP-JUN
- GSM7350175 NCI-H660 cells, siNC, ChIP-JUN
- GSM7350176 NCI-H660 cells, vehicle, ChIP-H3K4me2
- GSM7350177 NCI-H660 cells, vehicle, ATAC
- GSM7350178 LNCaP_FOXA2OE cells, vehicle, ChIP-FOXA2
- GSM7350179 LNCaP_FOXA2OE cells, vehicle, ChIP-JUN
- GSM7350180 LNCaP cells, siFOXA1, ChIP-JUN
- GSM7350181 LNCaP cells, siNC, ChIP-JUN
- GSM7350182 PC3 cells, C12, ChIP-FOXA2
- GSM7350183 PC3 cells, ORY-1001, ChIP-FOXA2
- GSM7350184 PC3 cells, vehicle, ChIP-FOXA2
- GSM7350185 PC3 cells, siFOXA2, ChIP-FOSL1
- GSM7350186 PC3 cells, siFOXA2, ChIP-JUN
- GSM7350187 PC3 cells, siNC, ChIP-FOSL1
- GSM7350188 PC3 cells, siNC, ChIP-JUN
- GSM7350189 PC3 cells, vehicle, ChIP-H3K27AC
- GSM7350190 PC3 cells, vehicle, ATAC
- GSM8015521 LNCaP_FOXA2K265R cells, vehicle, ChIP-JUN
- GSM8015522 PC3 cells, vehicle,ChIP-FOXA2
- GSM8015523 PC3 cells,vehicle, ChIP-FOXA2
- GSM8080192 DKO cells, vehicle,ChIP-FOXA2
- GSM8080193 DKO cells, ORY-1001, ChIP-FOXA2
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