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IFNγ-induced memory in human macrophages is not sustained by epigenetic changes but the durability of the cytokine itself [CUT&Tag]

GSE294916 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 28 samples Submitted 2025/12/22 Platform GPL34281
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 28 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
28 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.
Paper
IFNγ-induced memory in human macrophages is sustained by the durability of cytokine signaling itselfThe Journal of experimental medicine · 2026
Summary (written by the submitters)
Macrophages, as key sentinel cells of the innate immune system, can retain memory of prior stimulus exposure. Interferon gamma (IFNγ) plays a central role in maintaining trained immunity in vivo and can induce potent memory in macrophages. Such memory is associated with the formation of de novo enhancers that alter gene expression responses to subsequent stimuli.
Read the full summary ↓
However, how such enhancers are maintained after cytokine exposure remains unclear. We report that durable IFNγ-induced enhancers can last for days after cytokine washout, yet the underlying persistence mechanism is not cell-intrinsic. IFNγ-treated macrophages continue to exhibit JAK/STAT signaling days after cytokine removal. Blocking IFNγ signaling with a JAK inhibitor or anti-IFNγ neutralizing antibodies after cytokine removal is sufficient to reverse IFNγ-induced enhancers and erase the potentiated state of the treated macrophages. Our findings suggest that epigenetic changes in macrophages do not inherently encode innate immune memory or a “potentiated” macrophage state, but that rather epigenetic changes are themselves dependent on ongoing cytokine signaling. These findings suggest new possibilities for pharmacologic interventions to reverse aberrantly trained immune states associated with pathology.
Published in
IFNγ-induced memory in human macrophages is sustained by the durability of cytokine signaling itself
Gorin A, Niu S, Harriott N et al. · The Journal of experimental medicine 2026 · PMID 41706052 · doi:10.1084/jem.20250976
This dataset
Open GSE294916 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 GSE294916_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 PRJNA1252037 and SRA study SRP579508. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41706052) ↗
Study design
12 conditions, mostly in duplicate
Subject2_H3K4me1_CT_D0_unstim ×3 Subject2_H3K4me1_CT_D0_IFNy ×3 Subject2_H3K4me1_CT_D4_IFNy ×3 Subject2_H3K4me1_CT_D4_IFNy_rux ×3 Subject1_H3K4me1_CT_D0_unstim ×2 Subject1_H3K4me1_CT_D0_IFNy ×2 Subject1_H3K4me1_CT_D0_LPS ×2 Subject1_H3K4me1_CT_D0_LPS_rux ×2 +4 more

Supports a between-group comparison across 28 samples.

How we read this: 12 replicated groups read from 28 sample titles; they account for 28 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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