Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity
| العنوان: | Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity |
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| المؤلفون: | James E. Hudson, Arianna Sabò, James Rae, Gerard I. Evan, Deborah L. Burkhart, Bruno Amati, Robert G. Parton, Vera Pendino, Catherine H. Wilson, Megan Bywater, Enzo R. Porrello, Theresia R. Kress, Trevor D. Littlewood, Jasmin Straube, Gregory A. Quaife-Ryan |
| المساهمون: | Burkhart, Deborah L. [0000-0002-7457-6032], Sabò, Arianna [0000-0002-9542-0045], Pendino, Vera [0000-0001-9147-4161], Quaife-Ryan, Gregory A. [0000-0002-0012-9934], Parton, Robert G. [0000-0002-7494-5248], Amati, Bruno [0000-0002-2958-1799], Littlewood, Trevor D. [0000-0003-3475-1462], Evan, Gerard I. [0000-0003-0412-1216], Wilson, Catherine H. [0000-0002-5333-0295], Apollo - University of Cambridge Repository, Wilson, Catherine [0000-0002-5333-0295], Littlewood, Trevor [0000-0003-3475-1462], Evan, Gerard [0000-0003-0412-1216] |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Transcription, Genetic, Positive Transcriptional Elongation Factor B, General Physics and Astronomy, RNA polymerase II, 13/1, Mice, 0302 clinical medicine, Transcription (biology), 631/337/572, 38/23, Gene expression, Myocyte, Myocytes, Cardiac, Proto-Oncogene Proteins c-myc, Phosphorylation, lcsh:Science, Multidisciplinary, biology, Cyclin T, article, Chromatin, Cell biology, 13/31, Organ Specificity, 030220 oncology & carcinogenesis, 64/60, 631/67/70, Transcription, Protein Binding, Transcriptional Activation, Cell division, Science, 631/80/641, 13/106, General Biochemistry, Genetics and Molecular Biology, 38/91, 03 medical and health sciences, Animals, Cancer models, Cell Proliferation, Myocardium, General Chemistry, 45/15, 030104 developmental biology, 13/51, 14/63, biology.protein, Oncogene MYC, lcsh:Q, 14/28 |
| الوصف: | It is unclear why some tissues are refractory to the mitogenic effects of the oncogene Myc. Here we show that Myc activation induces rapid transcriptional responses followed by proliferation in some, but not all, organs. Despite such disparities in proliferative response, Myc is bound to DNA at open elements in responsive (liver) and non-responsive (heart) tissues, but fails to induce a robust transcriptional and proliferative response in the heart. Using heart as an exemplar of a non-responsive tissue, we show that Myc-driven transcription is re-engaged in mature cardiomyocytes by elevating levels of the positive transcription elongation factor (P-TEFb), instating a large proliferative response. Hence, P-TEFb activity is a key limiting determinant of whether the heart is permissive for Myc transcriptional activation. These data provide a greater understanding of how Myc transcriptional activity is determined and indicate modification of P-TEFb levels could be utilised to drive regeneration of adult cardiomyocytes for the treatment of heart myopathies. Levels of the transcription factor Myc are deregulated in a range of different cancers. Here the authors show that Myc induces rapid transcriptional responses in some mouse tissues (liver), but not others (heart), and that transcriptional and proliferative responses in cardiomyocytes depend on the positive transcription elongation factor (P-TEFb). |
| وصف الملف: | application/pdf; application/zip; text/xml |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::94985bdce6d77e286a080a18857a8c4d https://doaj.org/article/6242a1a22a8f47f48a5d16c07381d895 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....94985bdce6d77e286a080a18857a8c4d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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