Asymmetry between Activation and Deactivation during a Transcriptional Pulse

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Lee Dunham
  • Hiroshi Momiji
  • Claire Harper
  • Kirsty Hey
  • Anne Mcnamara
  • Karen Featherstone
  • David Rand
  • Bärbel Finkenstädt
  • Michael White

Abstract

Transcription in eukaryotic cells occurs in genespecific 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.

Bibliographical metadata

Original languageEnglish
Article numbere5
Pages (from-to)646-653
Number of pages8
JournalCell Systems
Volume5
Issue number6
Early online date15 Nov 2017
DOIs
Publication statusPublished - 27 Dec 2017