GEO series

PU.1 Eviction at Lymphocyte-Specific Chromatin Domains Mediates Glucocorticoid Response in Acute Lymphoblastic Leukemia

GSE236085 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 21 samples Submitted 2024/10/08 Platform GPL16791Platform GPL28038

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 21 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)
Topic: Acute lymphoblastic leukemiaThis series is part of our curated briefing on it.
Samples: 21 samples: 21 samples, each with a distinct title — no replicated groupsGroups 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: PU.1 eviction at lymphocyte-specific chromatin domains mediates glucocorticoid response in acute lymphoblastic leukemiaNature communications · 2024

Summary (written by the submitters)

Glucocorticoids are an essential part of many multi-agent treatment regimens for lymphoid malignancies where the emergence of glucocorticoid resistance is a significant barrier to a cure. We have previously identified that aberrant chromatin accessibility, at lymphocyte-specific glucocorticoid-response elements (GREs), is associated with drug resistance in acute lymphoblastic leukaemia (ALL).

Read the full summary ↓

To gain a deeper understanding of regulatory mechanisms leading to these epigenetic alterations, we conducted a multi-omics study, to examine changes in chromatin conformation, following the in-vivo treatment of patient-derived xenografts (PDXs) with glucocorticoid i.e., dexamethasone (DEX). We found that glucocorticoid treatment led to distinct patterns of topological associated domains (TADs) in DEX sensitive and resistant ALLs. Pre-treatment, these TADs were primed by a development-related pioneer transcription factor PU.1, which also occupied GREs in glucocorticoid sensitive but not resistant ALLs. PU.1 binding was associated with lymphocyte-specific activation of GREs and GRE-interacting super-enhancers within the TADs. Furthermore, the PU.1-associated TADs modulated epigenetics and promoted expression of multiple genes, including BIM, ZBTB16, RASA1 and other genes mediating glucocorticoid-induced apoptosis in ALL. The inhibition of PU.1 enhanced sensitivity of ALL cells to glucocorticoid treatment. Overall, this study illustrated a link between the lineage-specific efficiency of glucocorticoids and the developmental epigenetic modulators and provides insights into the role of fundamental epigenetics in clinical practice.

Published in

PU.1 eviction at lymphocyte-specific chromatin domains mediates glucocorticoid response in acute lymphoblastic leukemia

Beck D, Cao H, Tian F et al. · Nature communications 2024 · PMID 39516193 · doi:10.1038/s41467-024-54096-2

This dataset

Open GSE236085 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Acute lymphoblastic leukemia landscape →

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 GSE236085_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 PRJNA988808 and SRA study SRP446362. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39516193) ↗

Study design

21 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 21 sample titles: 21 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

GSM7518070 HiC_1 ALL50C
GSM7518071 HiC_2 ALL54C
GSM7518072 HiC_3 ALL50D
GSM7518073 HiC_4 ALL54D
GSM7518074 ChIPSeq_1_H3K4me1_ALL50C
GSM7518075 ChIPSeq_2_H3K4me1_ALL54C
GSM7518076 ChIPSeq_3_H3K4me1_ALL50D
GSM7518077 ChIPSeq_4_H3K4me1_ ALL54D
GSM7518078 ChIPSeq_5_EBF1_E50C
GSM7518079 ChIPSeq_6_EBF1_E54C
GSM7518080 ChIPSeq_7_EBF1_E50D
GSM7518081 ChIPSeq_8_EBF1_E54D
GSM7518082 ChIPSeq_9_SPI1_P50C
GSM7518083 ChIPSeq_10_SPI1_P54C
GSM7518084 ChIPSeq_11_SPI1_P50D
GSM7518085 ChIPSeq_12_SPI1_P54D
GSM8452715 KOPN8_IgG
GSM8452716 KOPN8_Ctrl_PU.1
GSM8452717 KOPN8_DB2313_PU.1
GSM8452718 KOPN8_Dex_PU.1
GSM8452719 KOPN8_Combo_PU.1

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.