Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity
| Autor: | 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 |
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| Přispěvatelé: | 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] |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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