Reactivation of Myc transcription in the mouse heart unlocks its proliferative capacity.
Animals
Cell Proliferation
/ genetics
Chromatin
/ metabolism
Cyclin T
/ metabolism
Mice
Myocardium
/ metabolism
Myocytes, Cardiac
/ metabolism
Organ Specificity
Phosphorylation
Positive Transcriptional Elongation Factor B
/ metabolism
Protein Binding
Proto-Oncogene Proteins c-myc
/ genetics
Transcription, Genetic
Transcriptional Activation
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 04 2020
14 04 2020
Historique:
received:
29
05
2019
accepted:
19
03
2020
entrez:
15
4
2020
pubmed:
15
4
2020
medline:
22
7
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32286286
doi: 10.1038/s41467-020-15552-x
pii: 10.1038/s41467-020-15552-x
pmc: PMC7156407
doi:
Substances chimiques
Chromatin
0
Cyclin T
0
Proto-Oncogene Proteins c-myc
0
Positive Transcriptional Elongation Factor B
EC 2.7.11.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1827Subventions
Organisme : Cancer Research UK
ID : 12077
Pays : United Kingdom
Organisme : Cancer Research UK
ID : RG78578
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A19013
Pays : United Kingdom
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