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FOXA2/AP-1 drives prostate cancer lineage plasticity [PDX ChIP-seq]

GSE232553 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 16 samples Submitted 2024/04/22 Platform GPL18573
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 16 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
16 samples: 5 conditions, mostly with about 4 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancerNature communications · 2024
Summary (written by the submitters)
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).
Read the full summary ↓
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
FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer
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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Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE232553_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA972716. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38851846) ↗
Study design
5 conditions, mostly with about 4 replicates each
PDX201.1, vehicle, ChIP-FOXA1, repeat ×4 PDX201.2, vehicle, ChIP-FOXA2, repeat ×4 PDX201.1, vehicle, ChIP-H3K27Ac, repeat ×3 PDX201.1, vehicle, ChIP-AR, repeat ×2 PDX201.2, vehicle, ChIP-H3K27Ac, repeat ×2 PDX201.1_PDX201.2_PDX_pooled_input ×1

Supports a between-group comparison across 15 samples.

How we read this: 5 replicated groups read from 16 sample titles; they account for 15 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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