GEO series
ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer (ChIP-Seq)
GSE259248
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing
36 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. ZBTB7A knockout and KDM5i cooperate to alter cell states with KDM5i decreasing basal-like and ZBTB7A knockout inducing mesenchymal-like gene expression patterns. Our work furthers our understanding of KDM5-mediated gene regulation in breast cancer and identifies key pathways that mediate sensitivity to KDM5 inhibition
Published in
DiCiaccio B, Seehawer M, Li Z et al.
· Cell reports 2024
· PMID 39570746
· doi:10.1016/j.celrep.2024.114991
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE259248_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 36 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1080532 and SRA study SRP491748. Searching any of these in the dataset finder brings you back here.
Study design
17 conditions, mostly in duplicate
SUM149, ROSA26KO, DMSO, KDM5A_IP, ×2
SUM149, ROSA26KO, DMSO, KDM5B_IP, ×2
SUM149, ROSA26KO, DMSO, H3K4me3_IP, ×2
SUM149, ROSA26KO, DMSO, ZBTB7A _IP, ×2
SUM149, ROSA26KO, 10 µM C70, KDM5A_IP, ×2
SUM149, ROSA26KO, 10 µM C70, KDM5B_IP, ×2
SUM149, ROSA26KO, 10 µM C70, H3K4me3_IP, ×2
SUM149, ROSA26KO, 10 µM C70, ZBTB7A _IP, ×2
+11 more
Supports a between-group comparison across 34 samples.
17 replicated groups read from 36 sample titles; they account for 34 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8112100 SUM149, ROSA26_KO, DMSO, Input_double_fixation
- GSM8112101 SUM149, ROSA26_KO, DMSO, Input_single_fixation
- GSM8112102 SUM149, ROSA26KO, DMSO, KDM5A_IP, rep1
- GSM8112103 SUM149, ROSA26KO, DMSO, KDM5A_IP, rep2
- GSM8112104 SUM149, ROSA26KO, DMSO, KDM5B_IP, rep1
- GSM8112105 SUM149, ROSA26KO, DMSO, KDM5B_IP, rep2
- GSM8112106 SUM149, ROSA26KO, DMSO, H3K4me3_IP, rep1
- GSM8112108 SUM149, ROSA26KO, DMSO, H3K4me3_IP, rep2
- GSM8112110 SUM149, ROSA26KO, DMSO, ZBTB7A _IP, rep1
- GSM8112112 SUM149, ROSA26KO, DMSO, ZBTB7A _IP, rep2
- GSM8112114 SUM149, ROSA26KO, 10 µM C70, KDM5A_IP, rep1
- GSM8112116 SUM149, ROSA26KO, 10 µM C70, KDM5A_IP, rep2
- GSM8112118 SUM149, ROSA26KO, 10 µM C70, KDM5B_IP, rep1
- GSM8112120 SUM149, ROSA26KO, 10 µM C70, KDM5B_IP, rep2
- GSM8112123 SUM149, ROSA26KO, 10 µM C70, H3K4me3_IP, rep1
- GSM8112125 SUM149, ROSA26KO, 10 µM C70, H3K4me3_IP, rep2
- GSM8112127 SUM149, ROSA26KO, 10 µM C70, ZBTB7A _IP, rep1
- GSM8112129 SUM149, ROSA26KO, 10 µM C70, ZBTB7A _IP, rep2
- GSM8112131 SUM149, KDM5AKO, DMSO, KDM5B_IP, rep1
- GSM8112133 SUM149, KDM5AKO, DMSO, H3K4me3_IP, rep1
- GSM8112134 SUM149, KDM5AKO, DMSO, ZBTB7A _IP, rep1
- GSM8112135 SUM149, KDM5AKO, DMSO, KDM5B_IP, rep2
- GSM8112136 SUM149, KDM5AKO, DMSO, H3K4me3_IP, rep2
- GSM8112137 SUM149, KDM5AKO, DMSO, ZBTB7A _IP, rep2
- GSM8112138 SUM149, KDM5BKO, DMSO, KDM5A_IP, rep1
- GSM8112139 SUM149, KDM5BKO, DMSO, H3K4me3_IP, rep1
- GSM8112140 SUM149, KDM5BKO, DMSO, ZBTB7A _IP, rep1
- GSM8112141 SUM149, KDM5BKO, DMSO, KDM5A_IP, rep2
- GSM8112142 SUM149, KDM5BKO, DMSO, H3K4me3_IP, rep2
- GSM8112143 SUM149, KDM5BKO, DMSO, ZBTB7A _IP, rep2
- GSM8112144 SUM149, ZBTB7AKO, DMSO, KDM5A_IP, rep1
- GSM8112145 SUM149, ZBTB7AKO, DMSO, KDM5B_IP, rep1
- GSM8112146 SUM149, ZBTB7AKO, DMSO, H3K4me3_IP, rep1
- GSM8112147 SUM149, ZBTB7AKO, DMSO, KDM5A_IP, rep2
- GSM8112148 SUM149, ZBTB7AKO, DMSO, KDM5B_IP, rep2
- GSM8112149 SUM149, ZBTB7AKO, DMSO, H3K4me3_IP, rep2
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