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Cited by 238

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms

Open access
Allen, Mary Ann, Andrysik, Zdenek, Dengler, Veronica L, Mellert, Hestia S, Guarnieri, Anna, Freeman, Justin A, Sullivan, Kelly D, Galbraith, Matthew D, Luo, Xin, Kraus, W Lee, Dowell, Robin D, Espinosa, Joaquin M·2014·eLife
DOI 10.7554/elife.02200
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Abstract

The p53 transcription factor is a potent suppressor of tumor growth. We report here an analysis of its direct transcriptional program using Global Run-On sequencing (GRO-seq). Shortly after MDM2 inhibition by Nutlin-3, low levels of p53 rapidly activate ∼200 genes, most of them not previously established as direct targets. This immediate response involves all canonical p53 effector pathways, including apoptosis. Comparative global analysis of RNA synthesis vs steady state levels revealed that microarray profiling fails to identify low abundance transcripts directly activated by p53. Interestingly, p53 represses a subset of its activation targets before MDM2 inhibition. GRO-seq uncovered a plethora of gene-specific regulatory features affecting key survival and apoptotic genes within the p53 network. p53 regulates hundreds of enhancer-derived RNAs. Strikingly, direct p53 targets harbor pre-activated enhancers highly transcribed in p53 null cells. Altogether, these results enable the study of many uncharacterized p53 target genes and unexpected regulatory mechanisms.

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Research works printed but not linked: 38

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Cited by

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Metadata

Authors
Allen, M. A., Andrysik, Z., Dengler, V. L., Mellert, H. S., Guarnieri, A., Freeman, J. A., Sullivan, K. D., Galbraith, M. D., Luo, X., Kraus, W. L., Dowell, R. D., & Espinosa, J. M.
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2014-05-27
Volume
3
Pages
e02200-e02200
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.02200
OpenAlex
W1981974167
Cited by
238
References
14
FWCI
11.35
Type
journal article
Language
en
Open access
gold
Licence
Funders
  • Howard Hughes Medical Institute (Early Career Award)
  • National Institutes of Health (RO1 CA117907-07, 2T15 LM009451)
  • Butcher Foundation
  • Boettcher Foundation
  • National Science Foundation (MCB1243522)
  • American Cancer Society

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CoChat. (2026). Citation check: Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms. https://app.cochat.ai/papers/10.7554/elife.02200
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Allen, M. A., Andrysik, Z., Dengler, V. L., Mellert, H. S., Guarnieri, A., Freeman, J. A., Sullivan, K. D., Galbraith, M. D., Luo, X., Kraus, W. L., Dowell, R. D., & Espinosa, J. M. (2014). Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms. eLife. https://doi.org/10.7554/elife.02200

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