Thermodynamic model of gene regulation for the Or59b olfactory receptor in Drosophila

PLoS Comput Biol. 2019 Jan 17;15(1):e1006709. doi: 10.1371/journal.pcbi.1006709. eCollection 2019 Jan.

Abstract

Complex eukaryotic promoters normally contain multiple cis-regulatory sequences for different transcription factors (TFs). The binding patterns of the TFs to these sites, as well as the way the TFs interact with each other and with the RNA polymerase (RNAp), lead to combinatorial problems rarely understood in detail, especially under varying epigenetic conditions. The aim of this paper is to build a model describing how the main regulatory cluster of the olfactory receptor Or59b drives transcription of this gene in Drosophila. The cluster-driven expression of this gene is represented as the equilibrium probability of RNAp being bound to the promoter region, using a statistical thermodynamic approach. The RNAp equilibrium probability is computed in terms of the occupancy probabilities of the single TFs of the cluster to the corresponding binding sites, and of the interaction rules among TFs and RNAp, using experimental data of Or59b expression to tune the model parameters. The model reproduces correctly the changes in RNAp binding probability induced by various mutation of specific sites and epigenetic modifications. Some of its predictions have also been validated in novel experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Drosophila / genetics*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Female
  • Gene Expression Regulation / genetics*
  • Male
  • Mutation / genetics
  • Promoter Regions, Genetic / genetics
  • Receptors, Odorant / genetics*
  • Receptors, Odorant / metabolism
  • Systems Biology
  • Thermodynamics

Substances

  • Chromatin
  • Drosophila Proteins
  • OR59B protein, Drosophila
  • Receptors, Odorant
  • DNA-Directed RNA Polymerases

Grants and funding

S. J. acknowledges support from Swedish Research Council (VR, grant n. 2016-06726). C.A. acknowledges support from the Swedish Foundation for Strategic Research (SSF, grant n. SB16-0011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.