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EP300/CREBBP acetyltransferase inhibition limits steroid receptor and FOXA1 signaling in prostate cancer cells (ChIP-seq)

GSE245967 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 90 samples Submitted 2024/03/14 Platform GPL18573Platform GPL30173
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 90 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
90 samples: 38 conditions, mostly in duplicateGroups 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
EP300/CREBBP acetyltransferase inhibition limits steroid receptor and FOXA1 signaling in prostate cancer cellsCellular and molecular life sciences : CMLS · 2024
Summary (written by the submitters)
The androgen receptor (AR) serves as the primary target for therapeutic intervention in prostate cancer (PCa), and AR-targeted treatments constitute the cornerstone of clinical management for this malignancy. Nevertheless, their effectiveness is often compromised by the emergence of resistance mechanisms. These resistant forms of PCa persist in activating AR signaling, highlighting the urgent need for new therapeutic strategies to combat therapy-resistant PCa.
Read the full summary ↓
Resistance to AR-targeted therapies can manifest through a multitude of mechanisms, including the overexpression of AR splice variants and altered activities of other transcription factors, such as the glucocorticoid receptor (GR) and FOXA1. A shared characteristic among these transcription factors is their dependence on a common set of coregulators, with EP300/CREBBP being a prominent example. This suggests a compelling rationale for employing coregulatory-targeted therapies in the management of treatment-resistant PCa. Here, we aimed to explore the impact of EP300/CREBBP acetyltransferase inhibition on steroid receptor and FOXA1 signaling in PCa cells, employing genome-wide techniques. Our findings illuminate that EP300/CREBBP inhibition exerts a substantial disruptive effect on the AR-regulated transcriptome and receptor chromatin binding, primarily by downregulating the AR-gene. Similarly, the transcriptome regulated by GR and the chromatin binding of the receptor were also hindered, although this was not associated with decreased GR expression levels. Instead, EP300/CREBBP acetyltransferase inhibition leads to a significant reduction in FOXA1 chromatin binding, consequently constraining GR signaling. In summary, our results emphasize how EP300/CREBBP acetyltransferase inhibition distinctly curtails the signaling activities of oncogenic transcription factors, underscoring the potential effectiveness of coregulatory-targeted therapies in PCa.
Published in
EP300/CREBBP acetyltransferase inhibition limits steroid receptor and FOXA1 signaling in prostate cancer cells
Huttunen J, Aaltonen N, Helminen L et al. · Cellular and molecular life sciences : CMLS 2024 · PMID 38564048 · doi:10.1007/s00018-024-05209-z
This dataset
Open GSE245967 in finder → Find more human ChIP / ATAC / CUT&Tag datasets →
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 GSE245967_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 PRJNA1030765 and SRA study SRP467776. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38564048) ↗
Study design
38 conditions, mostly in duplicate
VCaP_GR_DMSO_Dex ×4 VCaP_GR_A485_Dex ×4 VCaP_GR_ENZ3w_DMSO_Dex ×4 VCaP_GR_ENZ3w_A485_Dex ×4 22Rv1_AR_DMSO_DHT ×2 22Rv1_AR_A485_DHT ×2 22Rv1_GR_DMSO_Dex ×2 22Rv1_GR_A485_Dex ×2 +36 more

Supports a between-group comparison across 84 samples.

How we read this: 38 replicated groups read from 90 sample titles; they account for 84 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

+ 50 more — browse all 90 samples with per-sample file links →

Datasets on a similar topic

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