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

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


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.

MeSH terms

  • Chromatin Immunoprecipitation
  • DNA / metabolism*
  • DNA Damage*
  • Gene Expression Profiling*
  • Humans
  • MCF-7 Cells
  • Models, Theoretical
  • Protein Binding
  • Sequence Analysis, RNA
  • Transcription, Genetic*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • Tumor Suppressor Protein p53
  • DNA