GEO series

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

GSE291224 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 22 samples Submitted 2026/03/03 Platform GPL24676

Summary

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. 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

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Direct links to NCBI, no account and no request form: the whole study as GSE291224_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 22 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads 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.

8 replicated groups read from 22 sample titles; they account for 22 of them. Check it against the sample list below before relying on it.

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