Broadly heterogeneous activation of the master regulator for sporulation in Bacillus subtilis
- 19 April 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 107 (18), 8486-8491
- https://doi.org/10.1073/pnas.1002499107
Abstract
A model system for investigating how developmental regulatory networks determine cell fate is spore formation in Bacillus subtilis. The master regulator for sporulation is Spo0A, which is activated by phosphorylation via a phosphorelay that is subject to three positive feedback loops. The ultimate decision to sporulate is, however, stochastic in that only a portion of the population sporulates even under optimal conditions. It was previously assumed that activation of Spo0A and hence entry into sporulation is subject to a bistable switch mediated by one or more feedback loops. Here we reinvestigate the basis for bimodality in sporulation. We show that none of the feedback loops is rate limiting for the synthesis and phosphorylation of Spo0A. Instead, the loops ensure a just-in-time supply of relay components for rising levels of phosphorylated Spo0A, with phosphate flux through the relay being limiting for Spo0A activation and sporulation. In addition, genes under Spo0A control did not exhibit a bimodal pattern of expression as expected for a bistable switch. In contrast, we observed a highly heterogeneous pattern of Spo0A activation that increased in a nonlinear manner with time. We present a computational model for the nonlinear increase and propose that the phosphorelay is a noise generator and that only cells that attain a threshold level of phosphorylated Spo0A sporulate.Keywords
This publication has 26 references indexed in Scilit:
- Parallel pathways of repression and antirepression governing the transition to stationary phase in Bacillus subtilisProceedings of the National Academy of Sciences of the United States of America, 2008
- Nature, Nurture, or Chance: Stochastic Gene Expression and Its ConsequencesCell, 2008
- Bistability and biofilm formation in Bacillus subtilisMolecular Microbiology, 2007
- Model-based Definition of Population Heterogeneity and Its Effects on Metabolism in Sporulating Bacillus subtilisThe Journal of Biochemistry, 2007
- Engulfment during sporulation in Bacillus subtilis is governed by a multi‐protein complex containing tandemly acting autolysinsMolecular Microbiology, 2007
- Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noiseNature, 2006
- Phosphatases modulate the bistable sporulation gene expression pattern in Bacillus subtilisMolecular Microbiology, 2005
- Synergistic Kinetic Interactions between Components of the Phosphorelay Controlling Sporulation in Bacillus subtilisBiochemistry, 1998
- Post‐transcriptional control of a sporulation regulatory gene encoding transcription factor σH in Bacillus subtilisMolecular Microbiology, 1991
- Exact stochastic simulation of coupled chemical reactionsThe Journal of Physical Chemistry, 1977