ArticleNucleic acids research2017
BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
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- Gαq-Stimulated Gene Expression Is Insensitive to Bromo Extra Terminal Domain Inhibitors in HEK 293 Cells.International journal of molecular sciences · 2025Article
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- Integrating network pharmacology and experimental validation to uncover the synergistic effects of Huangqi ()-Ezhu () with 5-fluorouracil in colorectal cancer models.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Bromodomain Proteins Epigenetically Regulate the Mitotically Associated lncRNA MANCR in Triple Negative Breast Cancer Cells.Critical reviews in eukaryotic gene expression · 2024Article
- Inhibition of bromodomain-containing protein 4 enhances the migration of esophageal squamous cell carcinoma cells by inducing cell autophagy.World journal of gastrointestinal oncology · 2022Article
- Exploring the potential of eRNAs in cancer immunotherapy.Molecular therapy oncolytics · 2022Article
- Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance.International journal of molecular sciences · 2022Article
- SWAN pathway-network identification of common aneuploidy-based oncogenic drivers.Nucleic acids research · 2022Article
- Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022Review
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- Effects of Selenium on MAC-T Cells in Bovine Mastitis: Transcriptome Analysis of Exosomal mRNA Interactions.Biological trace element research · 2021Article
- The emerging role of BET inhibitors in breast cancer.Breast (Edinburgh, Scotland) · 2020Review
- Genomic Binding Patterns of Forkhead Box Protein O1 Reveal Its Unique Role in Cardiac Hypertrophy.Circulation · 2020Article
- p53-R273H promotes cancer cell migration via upregulation of neuraminidase-1.Journal of Cancer · 2020Article
- Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions.Nature communications · 2019Article
- p63 at the Crossroads between Stemness and Metastasis in Breast Cancer.International journal of molecular sciences · 2019Review
- Targeting the BRD4/FOXO3a/CDK6 axis sensitizes AKT inhibition in luminal breast cancer.Nature communications · 2018Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
Bromodomain-containing protein 4 (BRD4) is a member of the bromo- and extraterminal (BET) domain-containing family of epigenetic readers which is under intensive investigation as a target for anti-tumor therapy. BRD4 plays a central role in promoting the expression of select subsets of genes including many driven by oncogenic transcription factors and signaling pathways. However, the role of BRD4 and the effects of BET inhibitors in non-transformed cells remain mostly unclear. We demonstrate that BRD4 is required for the maintenance of a basal epithelial phenotype by regulating the expression of epithelial-specific genes including TP63 and Grainy Head-like transcription factor-3 (GRHL3) in non-transformed basal-like mammary epithelial cells. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription. Motif analyses of cell context-specific BRD4-enriched regions predicted the involvement of FOXO transcription factors. Consistently, activation of FOXO1 function via inhibition of EGFR-AKT signaling promoted the expression of TP63 and GRHL3. Moreover, activation of Src kinase signaling and FOXO1 inhibition decreased the expression of FOXO/BRD4 target genes. Together, our findings support a function for BRD4 in promoting basal mammary cell epithelial differentiation, at least in part, by regulating FOXO factor function on enhancers to activate TP63 and GRHL3 expression.
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