p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network
We report that p73 is expressed in multiciliated cells (MCCs), is required for MCC differentiation, and directly regulates transcriptional modulators of multiciliogenesis. Loss of ciliary biogenesis provides a unifying mechanism for many phenotypes observed in p73 knockout mice including hydrocephal...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716301383 |
| _version_ | 1819018864199991296 |
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| author | Clayton B. Marshall Deborah J. Mays J. Scott Beeler Jennifer M. Rosenbluth Kelli L. Boyd Gabriela L. Santos Guasch Timothy M. Shaver Lucy J. Tang Qi Liu Yu Shyr Bryan J. Venters Mark A. Magnuson Jennifer A. Pietenpol |
| author_facet | Clayton B. Marshall Deborah J. Mays J. Scott Beeler Jennifer M. Rosenbluth Kelli L. Boyd Gabriela L. Santos Guasch Timothy M. Shaver Lucy J. Tang Qi Liu Yu Shyr Bryan J. Venters Mark A. Magnuson Jennifer A. Pietenpol |
| author_sort | Clayton B. Marshall |
| collection | DOAJ |
| description | We report that p73 is expressed in multiciliated cells (MCCs), is required for MCC differentiation, and directly regulates transcriptional modulators of multiciliogenesis. Loss of ciliary biogenesis provides a unifying mechanism for many phenotypes observed in p73 knockout mice including hydrocephalus; hippocampal dysgenesis; sterility; and chronic inflammation/infection of lung, middle ear, and sinus. Through p73 and p63 ChIP-seq using murine tracheal cells, we identified over 100 putative p73 target genes that regulate MCC differentiation and homeostasis. We validated Foxj1, a transcriptional regulator of multiciliogenesis, and many other cilia-associated genes as direct target genes of p73 and p63. We show p73 and p63 are co-expressed in a subset of basal cells and suggest that p73 marks these cells for MCC differentiation. In summary, p73 is essential for MCC differentiation, functions as a critical regulator of a transcriptome required for MCC differentiation, and, like p63, has an essential role in development of tissues. |
| first_indexed | 2024-12-21T03:26:11Z |
| format | Article |
| id | doaj.art-60e7056b5c994e80bcb344c1e1c7bb07 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T03:26:11Z |
| publishDate | 2016-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-60e7056b5c994e80bcb344c1e1c7bb072022-12-21T19:17:36ZengElsevierCell Reports2211-12472016-03-0114102289230010.1016/j.celrep.2016.02.035p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene NetworkClayton B. Marshall0Deborah J. Mays1J. Scott Beeler2Jennifer M. Rosenbluth3Kelli L. Boyd4Gabriela L. Santos Guasch5Timothy M. Shaver6Lucy J. Tang7Qi Liu8Yu Shyr9Bryan J. Venters10Mark A. Magnuson11Jennifer A. Pietenpol12Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USADepartment of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USACenter for Quantitative Sciences, Vanderbilt University, Nashville, TN 37232, USAVanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USAVanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USAVanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USAWe report that p73 is expressed in multiciliated cells (MCCs), is required for MCC differentiation, and directly regulates transcriptional modulators of multiciliogenesis. Loss of ciliary biogenesis provides a unifying mechanism for many phenotypes observed in p73 knockout mice including hydrocephalus; hippocampal dysgenesis; sterility; and chronic inflammation/infection of lung, middle ear, and sinus. Through p73 and p63 ChIP-seq using murine tracheal cells, we identified over 100 putative p73 target genes that regulate MCC differentiation and homeostasis. We validated Foxj1, a transcriptional regulator of multiciliogenesis, and many other cilia-associated genes as direct target genes of p73 and p63. We show p73 and p63 are co-expressed in a subset of basal cells and suggest that p73 marks these cells for MCC differentiation. In summary, p73 is essential for MCC differentiation, functions as a critical regulator of a transcriptome required for MCC differentiation, and, like p63, has an essential role in development of tissues.http://www.sciencedirect.com/science/article/pii/S2211124716301383 |
| spellingShingle | Clayton B. Marshall Deborah J. Mays J. Scott Beeler Jennifer M. Rosenbluth Kelli L. Boyd Gabriela L. Santos Guasch Timothy M. Shaver Lucy J. Tang Qi Liu Yu Shyr Bryan J. Venters Mark A. Magnuson Jennifer A. Pietenpol p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network Cell Reports |
| title | p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network |
| title_full | p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network |
| title_fullStr | p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network |
| title_full_unstemmed | p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network |
| title_short | p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network |
| title_sort | p73 is required for multiciliogenesis and regulates the foxj1 associated gene network |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716301383 |
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