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Nat Struct Mol Biol. 2017 Oct;24(10):840-847. doi: 10.1038/nsmb.3452. Epub 2017 Aug 21.

p53 pulses lead to distinct patterns of gene expression albeit similar DNA-binding dynamics.

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Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.


The dynamics of transcription factors play important roles in a variety of biological systems. However, the mechanisms by which these dynamics are decoded into different transcriptional responses are not well understood. Here we focus on the dynamics of the tumor-suppressor protein p53, which exhibits a series of pulses in response to DNA damage. We performed time course RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) measurements to determine how p53 oscillations are linked with gene expression genome wide. We discovered multiple distinct patterns of gene expression in response to p53 pulses. Surprisingly, p53-binding dynamics were uniform across all genomic loci, even for genes that exhibited distinct mRNA dynamics. Using a mathematical model, supported by additional experimental measurements in response to sustained p53 input, we determined that p53 binds to and activates transcription of its target genes uniformly, whereas post-transcriptional mechanisms are responsible for the differences in gene expression dynamics.

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