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Combined inhibition of KAT6A/B and Menin reverses estrogen receptor-driven gene expression programs in breast cancer (ATAC-Seq)

GSE264724 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/04/30 Platform GPL18573
Summary
KAT6A is a histone acetyltransferase that is emerging as a therapeutic target in cancer, including estrogen receptor positive (ER+) breast cancer. We performed CRISPR screens to identify the chromatin adaptor Menin as a regulator of KAT6A inhibitor response. Co-treatment with KAT6A/B and Menin inhibitors had synergistic anti-proliferative effects in ER+, but not ER-, breast cancer lines. Our data revealed that KAT6A and Menin cooperatively regulate ER-driven gene expression and chromatin accessibility via direct effects on ESR1 expression and at ER target genes. KAT6A and Menin co-localize at promoters of ESR1 and ER-driven genes and combined KAT6A/B and Menin inhibition selectively displaced RNA Pol II from chromatin at these loci. Combined KAT6A/B and Menin inhibition was effective in ER+ patient-derived organoids and in models of endocrine resistance. KAT6A/B and Menin inhibitors are currently in clinical trials and have shown manageable toxicity profiles, underscoring the potential therapeutic relevance for ER+ breast cancer.
Published in
Combined inhibition of KAT6A/B and Menin reverses estrogen receptor-driven gene expression programs in breast cancer
Olsen SN, Anderson B, Hatton C et al. · Cell reports. Medicine 2025 · PMID 40516531 · doi:10.1016/j.xcrm.2025.102192
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Also filed as BioProject PRJNA1103852 and SRA study SRP503628. Searching any of these in the dataset finder brings you back here.

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