GEO series

Single-molecule chromatin configurations link transcription factor binding to expression in human cells [ChIP-seq]

GSE276514 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2024/09/10 Platform GPL21697

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 12 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: 12 samples: 10 distinct titles, 2 of them repeatedGroups 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: Single-molecule states link transcription factor binding to gene expressionNature · 2024

Summary (written by the submitters)

The binding of multiple transcription factors (TFs) to genomic enhancers activates gene expression in mammalian cells. However, the molecular details that link enhancer sequence to TF binding, promoter state, and gene expression levels remain opaque. We applied single-molecule footprinting (SMF) to measure the simultaneous occupancy of TFs, nucleosomes, and components of the transcription machinery on engineered enhancer/promoter constructs with variable numbers of TF binding sites for both a synthetic and an endogenous TF.

Read the full summary ↓

We find that activation domains enhance a TF’s capacity to compete with nucleosomes for binding to DNA in a BAF-dependent manner, TF binding on nucleosome-free DNA is consistent with independent binding between TFs, and average TF occupancy linearly contributes to promoter activation rates. We also decompose TF strength into separable binding and activation terms, which can be tuned and perturbed independently. Finally, we develop thermodynamic and kinetic models that quantitatively predict both the binding microstates observed at the enhancer and subsequent time-dependent gene expression. This work provides a template for quantitative dissection of distinct contributors to gene activation, including the activity of chromatin remodelers, TF activation domains, chromatin acetylation, TF concentration, TF binding affinity, and TF binding site configuration.

Published in

Single-molecule states link transcription factor binding to gene expression

Doughty BR, Hinks MM, Schaepe JM et al. · Nature 2024 · PMID 39567683 · doi:10.1038/s41586-024-08219-w

This dataset

Open GSE276514 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 GSE276514_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 PRJNA1071686 and SRA study SRP487205. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39567683) ↗

Study design

10 distinct titles, 2 of them repeated

ChIP_H3K27ac_dox_4xTetO_mESC_spike ×2 ChIP_H3K27ac_dox_p300_inhibitor_A485_4xTetO_m… ×2

How we read this: Read from 12 sample titles: 10 distinct titles with little repetition. 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

GSM8499756 ChIP_H3K27ac_dox_4xTetO_mESC_spike_rep1
GSM8499757 ChIP_H3K27ac_dox_4xTetO_mESC_spike_rep2
GSM8499758 ChIP_H3K27ac_dox_p300_inhibitor_A485_4xTetO_mESC_spike_rep1
GSM8499759 ChIP_H3K27ac_dox_p300_inhibitor_A485_4xTetO_mESC_spike_rep2
GSM8499760 L2487-Michaela_Dox_H3K27ac_rep1
GSM8499761 L2488-Michaela_Dox_H3K27ac_rep2
GSM8499762 L2489-Michaela_NoDox_H3K27ac_rep1
GSM8499763 L2490-Michaela_NoDox_H3K27ac_rep2
GSM8499764 L2493-Michaela_Dox_Pol2_4H8_rep1
GSM8499765 L2494-Michaela_Dox_Pol2_4H8_rep2
GSM8499766 L2495-Michaela_NoDox_Pol2_4H8_rep1
GSM8499767 L2496-Michaela_NoDox_Pol2_4H8_rep2

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