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ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer (scRNA-seq)

GSE263161 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2024/10/14 Platform GPL24676
Summary
We previously identified KDM5B, encoding a histone H3 lysine 4 (H3K4) demethylase, as an oncogene in estrogen receptor positive (ER+) breast cancer driving endocrine resistance. Here we describe that KDM5A is frequently amplified and overexpressed in basal breast tumors and is associated with chemotherapy resistance. Using CRISPR knockout viability screens -/+ KDM5 inhibition (KDM5i), we found that deletion of the transcription factor ZBTB7A and core SAGA complex increased sensitivity to KDM5i, whereas knockout of RHO-GTPases led to resistance. Integrated ChIP-seq and RNA-seq analyses revealed colocalization of ZBTB7A and KDM5s at promoters with high H3K4me3 signal and dependence of KDM5A binding on ZBTB7A. ZBTB7A knockout had a pleiotropic effect on transcriptional responses to KDM5i, in which it modulates the KDM5i-induced innate immune signaling and NF-kB-regulated genes.
Published in
ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer
DiCiaccio B, Seehawer M, Li Z et al. · Cell reports 2024 · PMID 39570746 · doi:10.1016/j.celrep.2024.114991
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Also filed as BioProject PRJNA1095998 and SRA study SRP499632. Searching any of these in the dataset finder brings you back here.

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