Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity

Megan J. Bywater, Deborah L. Burkhart, Jasmin Straube, Arianna Sabò, Vera Pendino, James E. Hudson, Gregory A. Quaife-Ryan, Enzo R. Porrello, James Rae, Robert G. Parton, Theresia R. Kress, Bruno Amati, Trevor D. Littlewood, Gerard I. Evan () and Catherine H. Wilson ()
Additional contact information
Megan J. Bywater: University of Cambridge
Deborah L. Burkhart: University of Cambridge
Jasmin Straube: QIMR Berghofer Medical Research Institute
Arianna Sabò: European Institute of Oncology (IEO) - IRCCS
Vera Pendino: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT)
James E. Hudson: QIMR Berghofer Medical Research Institute
Gregory A. Quaife-Ryan: QIMR Berghofer Medical Research Institute
Enzo R. Porrello: The Royal Children’s Hospital
James Rae: The University of Queensland
Robert G. Parton: The University of Queensland
Theresia R. Kress: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT)
Bruno Amati: European Institute of Oncology (IEO) - IRCCS
Trevor D. Littlewood: University of Cambridge
Gerard I. Evan: University of Cambridge
Catherine H. Wilson: University of Cambridge

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15552-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15552-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15552-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().