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ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE259252 | GEO | 2024/10/14

REPOSITORIES: GEO

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

Project description: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.

2024-10-14 | GSE263161 | GEO

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

2024-10-14 | GSE259249 | GEO

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

2024-10-14 | GSE259248 | GEO

ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer

Project description:ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer

| PRJNA1080529 | ENA

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

Project description:ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer (ChIP-Seq)

| PRJNA1080532 | ENA

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

Project description:ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer (RNA-Seq)

| PRJNA1080531 | ENA

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

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

| PRJNA1095998 | ENA

CDK7-dependent Transcriptional Addition in Basal-like Breast Cancer

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-05-21 | E-GEOD-69107 | biostudies-arrayexpress

ZBTB7A governs estrogen receptor alpha expression in breast cancer.

Project description:ZBTB7A, a member of the POZ/BTB and Krüppel (POK) family of transcription factors, has been shown to have a context-dependent role in cancer development and progression. The role of ZBTB7A in estrogen receptor alpha (ER?)-positive breast cancer is largely unknown. Approximately 70% of breast cancers are classified as ER?-positive. ER? carries out the biological effects of estrogen and its expression level dictates response to endocrine therapies and prognosis for breast cancer patients. In this study, we find that ZBTB7A transcriptionally regulates ER? expression in ER?-positive breast cancer cell lines by binding to the ESR1 promoter leading to increased transcription of ER?. Inhibition of ZBTB7A in ER?-positive cells results in decreased estrogen responsiveness as demonstrated by diminished estrogen-response element-driven luciferase reporter activity, induction of estrogen target genes, and estrogen-stimulated growth. We also report that ER? potentiates ZBTB7A expression via a post-translational mechanism, suggesting the presence of a positive feedback loop between ZBTB7A and ER?, conferring sensitivity to estrogen in breast cancer. Clinically, we find that ZBTB7A and ER? are often co-expressed in breast cancers and that high ZBTB7A expression correlates with improved overall and relapse-free survival for breast cancer patients. Importantly, high ZBTB7A expression predicts a more favorable outcome for patients treated with endocrine therapies. Together, these findings demonstrate that ZBTB7A contributes to the transcriptional program maintaining ER? expression and potentially an endocrine therapy-responsive phenotype in breast cancer.

| S-EPMC6161408 | biostudies-literature

CDK7-dependent Transcriptional Addiction in Basal-like Breast Cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-05-21 | GSE69107 | GEO