Genome-Wide Characterization of TAZ Binding Sites in Mammary Epithelial Cells
The transcriptional co-activator with PDZ binding motif (TAZ) is a key effector of the Hippo signaling pathway. We and others previously reported that high expression levels of TAZ are positively associated with decreased survival rates and shorter times to relapse in basal-like breast cancer (BLBC)...
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MDPI AG
2023-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/19/4713 |
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| author | Tao Liu Jiaojiao Zhou Yanmin Chen Jia Fang Song Liu Costa Frangou Hai Wang Jianmin Zhang |
| author_facet | Tao Liu Jiaojiao Zhou Yanmin Chen Jia Fang Song Liu Costa Frangou Hai Wang Jianmin Zhang |
| author_sort | Tao Liu |
| collection | DOAJ |
| description | The transcriptional co-activator with PDZ binding motif (TAZ) is a key effector of the Hippo signaling pathway. We and others previously reported that high expression levels of TAZ are positively associated with decreased survival rates and shorter times to relapse in basal-like breast cancer (BLBC) patients. The oncogenic activity of TAZ involves the regulation of diverse signal transduction pathways that direct processes such as cell proliferation, migration, and resistance to apoptosis, albeit through poorly characterized gene expression programs. Here, using a tet-inducible system in mammary epithelial MCF10A cells, we have characterized the TAZ-regulated transcription program using RNA sequencing in a temporal and spatial manner. We further identified global TAZ binding sites at different TAZ activation time points by chromatin immunoprecipitation (ChIP) sequencing analysis. We found that the vast majority of TAZ was rapidly localized in enhancer regions at the early TAZ activation time point and then gradually spread to promoter regions. TAZ bound to enhancer regions following a switch in potential TEAD and FOSL2 transcription factor motifs. Furthermore, the ATAC sequencing analysis indicated that TAZ activation led to chromatin structural alterations. Together, our results have revealed the landscape of genome-wide TAZ binding sites and may lead to improvements in the current understanding of how TAZ regulates the gene expression program that contributes to the development of breast cancer. |
| first_indexed | 2024-03-10T21:47:37Z |
| format | Article |
| id | doaj.art-6bda83eacbc7479d986cc5f472c8ac97 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:47:37Z |
| publishDate | 2023-09-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6bda83eacbc7479d986cc5f472c8ac972023-11-19T14:09:30ZengMDPI AGCancers2072-66942023-09-011519471310.3390/cancers15194713Genome-Wide Characterization of TAZ Binding Sites in Mammary Epithelial CellsTao Liu0Jiaojiao Zhou1Yanmin Chen2Jia Fang3Song Liu4Costa Frangou5Hai Wang6Jianmin Zhang7Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Elm Street, Buffalo, NY 14203, USADepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Elm Street, Buffalo, NY 14203, USADepartment of Cancer Genetics & Genomics, Roswell Park Comprehensive Cancer Center, Elm Street, Buffalo, NY 14203, USADepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Elm Street, Buffalo, NY 14203, USADepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Elm Street, Buffalo, NY 14203, USADepartment of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Elm Street, Buffalo, NY 14203, USADepartment of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Elm Street, Buffalo, NY 14203, USADepartment of Cancer Genetics & Genomics, Roswell Park Comprehensive Cancer Center, Elm Street, Buffalo, NY 14203, USAThe transcriptional co-activator with PDZ binding motif (TAZ) is a key effector of the Hippo signaling pathway. We and others previously reported that high expression levels of TAZ are positively associated with decreased survival rates and shorter times to relapse in basal-like breast cancer (BLBC) patients. The oncogenic activity of TAZ involves the regulation of diverse signal transduction pathways that direct processes such as cell proliferation, migration, and resistance to apoptosis, albeit through poorly characterized gene expression programs. Here, using a tet-inducible system in mammary epithelial MCF10A cells, we have characterized the TAZ-regulated transcription program using RNA sequencing in a temporal and spatial manner. We further identified global TAZ binding sites at different TAZ activation time points by chromatin immunoprecipitation (ChIP) sequencing analysis. We found that the vast majority of TAZ was rapidly localized in enhancer regions at the early TAZ activation time point and then gradually spread to promoter regions. TAZ bound to enhancer regions following a switch in potential TEAD and FOSL2 transcription factor motifs. Furthermore, the ATAC sequencing analysis indicated that TAZ activation led to chromatin structural alterations. Together, our results have revealed the landscape of genome-wide TAZ binding sites and may lead to improvements in the current understanding of how TAZ regulates the gene expression program that contributes to the development of breast cancer.https://www.mdpi.com/2072-6694/15/19/4713TAZbreast cancerTEADFOSL2ChIP-seqenhancer |
| spellingShingle | Tao Liu Jiaojiao Zhou Yanmin Chen Jia Fang Song Liu Costa Frangou Hai Wang Jianmin Zhang Genome-Wide Characterization of TAZ Binding Sites in Mammary Epithelial Cells Cancers TAZ breast cancer TEAD FOSL2 ChIP-seq enhancer |
| title | Genome-Wide Characterization of TAZ Binding Sites in Mammary Epithelial Cells |
| title_full | Genome-Wide Characterization of TAZ Binding Sites in Mammary Epithelial Cells |
| title_fullStr | Genome-Wide Characterization of TAZ Binding Sites in Mammary Epithelial Cells |
| title_full_unstemmed | Genome-Wide Characterization of TAZ Binding Sites in Mammary Epithelial Cells |
| title_short | Genome-Wide Characterization of TAZ Binding Sites in Mammary Epithelial Cells |
| title_sort | genome wide characterization of taz binding sites in mammary epithelial cells |
| topic | TAZ breast cancer TEAD FOSL2 ChIP-seq enhancer |
| url | https://www.mdpi.com/2072-6694/15/19/4713 |
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