Author
Listed:
- Amy Tarangelo
(Center for Childhood Cancer Research, Children’s Hospital of Philadelphia)
- Nathanael Lo
(Center for Childhood Cancer Research, Children’s Hospital of Philadelphia)
- Rebecca Teng
(Center for Childhood Cancer Research, Children’s Hospital of Philadelphia)
- Eunsun Kim
(Center for Childhood Cancer Research, Children’s Hospital of Philadelphia)
- Linh Le
(Center for Childhood Cancer Research, Children’s Hospital of Philadelphia)
- Deborah Watson
(Children’s Hospital of Philadelphia)
- Emma E. Furth
(Perelman School of Medicine, University of Pennsylvania)
- Pichai Raman
(Children’s Hospital of Philadelphia
School of Biomedical Engineering, Sciences and Health Systems, Drexel University)
- Ursula Ehmer
(University Hospital of Munich)
- Patrick Viatour
(Center for Childhood Cancer Research, Children’s Hospital of Philadelphia
Perelman School of Medicine, University of Pennsylvania)
Abstract
Changes in gene expression during tumorigenesis are often considered the consequence of de novo mutations occurring in the tumour. An alternative possibility is that the transcriptional response of oncogenic transcription factors evolves during tumorigenesis. Here we show that aberrant E2f activity, following inactivation of the Rb gene family in a mouse model of liver cancer, initially activates a robust gene expression programme associated with the cell cycle. Slowly accumulating E2f1 progressively recruits a Pontin/Reptin complex to open the chromatin conformation at E2f target genes and amplifies the E2f transcriptional response. This mechanism enhances the E2f-mediated transactivation of cell cycle genes and initiates the activation of low binding affinity E2f target genes that regulate non-cell-cycle functions, such as the Warburg effect. These data indicate that both the physiological and the oncogenic activities of E2f result in distinct transcriptional responses, which could be exploited to target E2f oncogenic activity for therapy.
Suggested Citation
Amy Tarangelo & Nathanael Lo & Rebecca Teng & Eunsun Kim & Linh Le & Deborah Watson & Emma E. Furth & Pichai Raman & Ursula Ehmer & Patrick Viatour, 2015.
"Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression,"
Nature Communications, Nature, vol. 6(1), pages 1-14, December.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10028
DOI: 10.1038/ncomms10028
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