Asymmetry between Activation and Deactivation during a Transcriptional Pulse

Lee S S Dunham, Hiroshi Momiji, Claire V Harper, Polly J Downton, Kirsty Hey, Anne McNamara, Karen Featherstone, David G Spiller, David A Rand, Bärbel Finkenstädt, Michael R H White, Julian R E Davis

Research output: Contribution to journalArticle

7 Citations (Scopus)
30 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)646-653.e5
JournalCell Systems
Volume5
Issue number6
Early online date15 Nov 2017
DOIs
Publication statusPublished - 27 Dec 2017

Keywords

  • Animals
  • Cell Line
  • Cyclic AMP/metabolism
  • Female
  • Genes, Reporter/genetics
  • Histone Deacetylases/metabolism
  • Human Growth Hormone/genetics
  • Humans
  • Luciferases/genetics
  • Models, Theoretical
  • United Kingdom
  • Prolactin/genetics
  • Rats
  • Single-Cell Analysis
  • Transcription, Genetic
  • Transcriptional Activation
  • pituitary
  • gene transcription
  • modeling
  • prolactin
  • growth hormone

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  • Cite this

    Dunham, L. S. S., Momiji, H., Harper, C. V., Downton, P. J., Hey, K., McNamara, A., Featherstone, K., Spiller, D. G., Rand, D. A., Finkenstädt, B., White, M. R. H., & Davis, J. R. E. (2017). Asymmetry between Activation and Deactivation during a Transcriptional Pulse. Cell Systems, 5(6), 646-653.e5. https://doi.org/10.1016/j.cels.2017.10.013