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The transcription-repression domain of the adenovirus E1A oncoprotein targets p300 at the promoter

Oncogene volume 27, pages 4446–4455 (2008)Cite this article

Abstract

Extensive mutational/functional analysis of the transcription-repression domain encoded in the N-terminal 80 amino acids of the adenovirus E1A 243R oncoprotein suggests a model for the molecular mechanism of E1A repression: E1A accesses transcriptional co-activators such as p300 on specific promoters and then interacts with TBP to disrupt the TBP–TATA complex. In support of this model, as reported here, a basal core promoter activated by tethering p300 is repressible by E1A at the promoter level as shown by chromatin immunoprecipitation (ChIP) analysis. Sequestration of p300 by E1A does not play a significant role, as indicated by dose-response measurements. Furthermore, when the core promoter is transcriptionally activated by tethering activation domains of several transcription factors that can recruit p300 (p65, MyoD, cMyb and TFE3), transcription is repressible by E1A. However, when the core promoter is activated by factors not known to recruit p300 (USF1 and USF2), transcription is resistant to E1A repression. Finally, tethering p300 to the non-repressible adenovirus major late promoter (MLP) renders it repressible by E1A. ChIP analysis shows that E1A occupies the repressed MLP. These findings provide support for the hypothesis that p300 can serve as a scaffold for the E1A repression domain to access specific cellular gene promoters involved in growth regulation.

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Acknowledgements

We thank Steve Weintraub, Douglas Dean, Antonio Postigo, Antonio Giordano, Michle Sawadogo and Kevin Struhl for the plasmid stocks. We also thank Steve Weintraub and Ling Zhao for critical reading of the manuscript and Carolyn Mulhall for valuable editorial assistance. This work was supported by Research Career Award AI-04739 and Public Health Service Grant CA29561 to MG from the National Institutes of Health.

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  1. Institute for Molecular Virology, Saint Louis University School of Medicine, St Louis, MO, USA

    M Green, N K Panesar & P M Loewenstein

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  1. M Green
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  2. N K Panesar
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  3. P M Loewenstein
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Correspondence to M Green.

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Green, M., Panesar, N. & Loewenstein, P. The transcription-repression domain of the adenovirus E1A oncoprotein targets p300 at the promoter. Oncogene 27, 4446–4455 (2008). https://doi.org/10.1038/onc.2008.85

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