Mechanical bounds to transcriptional noise

Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):13983-13988. doi: 10.1073/pnas.1612651113. Epub 2016 Nov 22.

Abstract

Over the past several decades it has been increasingly recognized that stochastic processes play a central role in transcription. Although many stochastic effects have been explained, the source of transcriptional bursting (one of the most well-known sources of stochasticity) has continued to evade understanding. Recent results have pointed to mechanical feedback as the source of transcriptional bursting, but a reconciliation of this perspective with preexisting views of transcriptional regulation is lacking. In this article, we present a simple phenomenological model that is able to incorporate the traditional view of gene expression within a framework with mechanical limits to transcription. By introducing a simple competition between mechanical arrest and relaxation copy number probability distributions collapse onto a shared universal curve under shifting and rescaling and a lower limit of intrinsic noise for any mean expression level is found.

Keywords: bursting noise; supercoiling; topoisomerase; transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • DNA Topoisomerases, Type I / physiology
  • DNA, Superhelical / metabolism
  • DNA, Superhelical / physiology
  • Gene Expression Regulation / physiology*
  • Humans
  • Mechanoreceptors / metabolism
  • Mechanoreceptors / physiology
  • Models, Biological
  • Models, Theoretical
  • Probability
  • RNA, Messenger / metabolism
  • Stochastic Processes
  • Transcription, Genetic / physiology
  • Transcriptional Activation / genetics
  • Transcriptional Activation / physiology*

Substances

  • DNA, Superhelical
  • RNA, Messenger
  • DNA Topoisomerases, Type I