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AF9/KLF2 gene regulatory circuit links histone lactylation to breast cancer metastasis [CUT&Tag]

GSE291224 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 22 samples Submitted 2026/03/03 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 22 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
Breast cancerThis series is part of our curated briefing on it.
Samples
22 samples: 8 conditions, mostly in triplicateGroups 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
AF9-KLF2 gene regulatory circuit links histone lactylation to metabolic reprogramming and breast cancer progressionCell reports · 2026
Summary (written by the submitters)
Histone lysine L-lactylation (hereafter referred to as histone Kla) is a novel epigenetic mark induced by glycolytic metabolism, serving as a link between metabolic reprogramming and epigenetic regulation. In this study, we uncover an epigenetic-genetic transcriptional regulatory circuit involving AF9 and KLF2 that drives luminal breast cancer progression.
Read the full summary ↓
AF9, identified as a reader of histone H3 lysine 9 lactylation (H3K9la), promotes KLF2 expression, while KLF2, functioning as a transcription factor for AF9, forms a positive feedback loop that amplifies lactylation-dependent effects. This circuit activates tumor-associated pathways, including TGFβ1, glucose and lactate transporters, and metabolic enzymes essential for glycolysis and serine biosynthesis, driving tumorigenesis and metastasis. Spatial and single-cell transcriptomics show AF9-positive tumor cells enriched in regions of active lactylation, correlated with immune evasion through interactions with M2 macrophages. Together, AF9, H3K9la, and KLF2 integrate metabolism, epigenetics, and signaling to promote tumor growth and metastasis, highlighting AF9's central role as a histone lactylation reader and a potential therapeutic target in breast cancer.
Published in
AF9-KLF2 gene regulatory circuit links histone lactylation to metabolic reprogramming and breast cancer progression
Ma H, Yuan M, Yang C et al. · Cell reports 2026 · PMID 42189684 · doi:10.1016/j.celrep.2026.117429
This dataset
Open GSE291224 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Breast cancer 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 GSE291224_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 PRJNA1232605 and SRA study SRP568309. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42189684) ↗
Study design
8 conditions, mostly in triplicate
AF9 ×3 Flag-AF9F28R ×3 Flag-AF9WT ×3 Flag-AF9G77A ×3 H3K9ac ×3 H3K9la ×3 Flag-vector ×2 Flag-KLF2 ×2

Supports a between-group comparison across 22 samples.

How we read this: 8 replicated groups read from 22 sample titles; they account for 22 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
More Breast cancer datasets

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