GEO series

An intronic region within FTO confers differentiation block in acute myeloid leukaemia through regulation of IRX3 and HOX [ChIP-seq re-analysis]

GSE225519 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 10 samples Submitted 2025/01/21 Platform GPL18573

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 10 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: 10 samples
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: Differentiation block in acute myeloid leukemia regulated by intronic sequences of FTOiScience · 2023

Summary (written by the submitters)

Transcription factors are key determinants in myeloid identity and differentiation fates and when mis- expressed or mutated, they cause a differentiation block, the cardinal feature of acute myeloid leukaemia (AML). The Forkhead family transcription factor FOXC1, is de-repressed in a lineage- inappropriate manner in approximately 30% of cases of HOXAhigh AML with functional consequences and prognostic significance.

Read the full summary ↓

The mechanisms by which FOXC1 is mis-expressed remain to be determined and they presumably belong to a network of transcription factors and chromatin proteins that represent attractive therapeutic targets in AML. We performed an integrative omics analysis using AML primary samples and discovered an active distal enhancer at the FOXC1 topologically associated domain (TAD) that is more acetylated, accessible and differentially interacts with FOXC1, positively regulating its expression in FOXC1high AML. Moreover, through integrated next generation sequencing and functional analysis, we identified SOX4 as one of the upstream regulators of FOXC1 in leukaemia, where it is broadly expressed and associated with a high level of differentiation block. SOX4 binds at multiple sites across the FOXC1 TAD and directly controls its expression. Genome wide, SOX4 is preferentially bound at sites of accessible and acetylated chromatin at both promoter regions and active enhancers of transcription factors genes that include FOXC1, where it acts as a transcription activator. Our studies reveal a set of regulatory elements that control FOXC1 expression and highlight the role of SOX4 as a transcriptional activator that promotes differentiation block in AML.

Published in

Differentiation block in acute myeloid leukemia regulated by intronic sequences of FTO

Camera F, Romero-Camarero I, Revell BH et al. · iScience 2023 · PMID 37539037 · doi:10.1016/j.isci.2023.107319

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 GSE225519_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 PRJNA936113 and SRA study SRP423172. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 37539037) ↗

Samples in this study

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+ 10 more — browse all 10 samples with per-sample file links →

Datasets on a similar topic

GSE226453 An intronic region within FTO confers differentiation block in acute myeloid leukaemia through regulation of IRX3 and HOX [RNA-seq re-analysis] 8 samples shares irx3, fto, hox, re-analysis, leukaemia, intronic, confers
GSE223792 An intronic region within FTO confers differentiation block in acute myeloid leukaemia through regulation of IRX3 and HOX 40 samples shares irx3, fto, hox, leukaemia, intronic, confers
GSE223790 An intronic region within FTO confers differentiation block in acute myeloid leukaemia through regulation of IRX3 and HOX [RNA-Seq] 8 samples shares irx3, fto, hox, leukaemia, intronic, confers
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