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Redirecting the pioneering function of FOXA1 with covalent small molecules [ATAC-seq]

GSE261801 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 29 samples Submitted 2024/03/26 Platform GPL30173
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 29 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
29 samples: 12 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.
Summary (written by the submitters)
Pioneer transcription factors (TFs) exhibit a special ability to bind to and open closed chromatin, facilitating engagement by other regulatory factors involved in gene activation or repression. Chemical probes are lacking for pioneer TFs, which has hindered their mechanistic investigation in cells. Here, we report electrophilic small molecules that stereoselectively and site-specifically bind the pioneer TF, FOXA1, at a cysteine (C258) within the forkhead DNA-binding domain.
Read the full summary ↓
We show that these covalent ligands react with FOXA1 in a DNA-dependent manner and rapidly remodel its pioneer activity in prostate cancer cells reflected in redistribution of FOXA1 binding across the genome and directionally correlated changes in chromatin accessibility. Motif analysis supports a mechanism where the covalent ligands relax the canonical DNA binding preference of FOXA1 by strengthening interactions with suboptimal ancillary sequences in predicted proximity to C258. Our findings reveal a striking plasticity underpinning the pioneering function of FOXA1 that can be controlled by small molecules.
This dataset
Open GSE261801 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 GSE261801_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 PRJNA1089114 and SRA study SRP496057. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
12 conditions, mostly in duplicate
22Rv1-parental, DMSO, ×3 22Rv1-parental, WX23, ×3 22Rv1-parental, WX43, ×3 22Rv1-parental, PladB, 10nM, ×3 22Rv1-parental, PladB, 100nM, ×3 22Rv1-FOXA1-WT, DMSO, ×2 22Rv1-FOXA1-WT, WX23, ×2 22Rv1-FOXA1-WT, PladB, ×2 +4 more

Supports a between-group comparison across 29 samples.

How we read this: 12 replicated groups read from 29 sample titles; they account for 29 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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