Asymmetry between Activation and Deactivation during a Transcriptional Pulse

Cell Syst. 2017 Dec 27;5(6):646-653.e5. doi: 10.1016/j.cels.2017.10.013. Epub 2017 Nov 15.


Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active "on-states," interspersed with periods of inactivity, but these "off-states" and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone or human prolactin promoters in a pituitary cell line. Subsequently, we applied a statistical variable-rate model of transcription, validated by single-molecule FISH, to estimate switching between transcriptional rates. Under the assumption that transcription can switch to any rate at any time, we found that transcriptional activation occurs predominantly as a single switch, whereas deactivation occurs with graded, stepwise decreases in transcription rate. Experimentally altering cAMP signalling with forskolin or chromatin remodelling with histone deacetylase inhibitor modifies the duration of defined transcriptional states. Our findings reveal transcriptional activation and deactivation as mechanistically independent, asymmetrical processes.

Keywords: gene transcription; growth hormone; modeling; pituitary; prolactin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cyclic AMP / metabolism
  • Female
  • Genes, Reporter / genetics
  • Histone Deacetylases / metabolism
  • Human Growth Hormone / genetics*
  • Humans
  • Luciferases / genetics
  • Models, Theoretical*
  • Pituitary Gland / physiology*
  • Prolactin / genetics*
  • Promoter Regions, Genetic / genetics
  • Rats
  • Single-Cell Analysis
  • Transcription, Genetic*
  • Transcriptional Activation


  • Human Growth Hormone
  • Prolactin
  • Cyclic AMP
  • Luciferases
  • Histone Deacetylases