Dual-Specificity Anti-sigma Factor Reinforces Control of Cell-Type Specific Gene Expression in Bacillus subtilis

• Type of Material: Article
• Authors: Monica Serrano, Universidade Nova de Lisboa; JinXin Gao, Emory University; Bota João, Universidade Nova de Lisboa; Ashley R. Bate, New York University; Jeffrey Meisner, Emory University; Patrick Eichenberger, New York University; Charles Moran Jr., Emory University; Adriano O. Henriques, Universidade Nova de Lisboa
• Language: English
• Date: 2015-03-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Serrano et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pgen.1005104
• Title of Journal or Parent Work: PLoS Genetics
• ISSN: 1553-7390
• Volume: 11
• Issue: 3
• Start Page: e1005104
• End Page: e1005104
• Grant/Funding Information: This work was supported by grants POCTI/BIA-BCM/60855/2004 and PEst-OE/EQB/LA0004/2011 from “Fundação para a Ciência e a Tecnologia” (FCT) to AOH and programme IF (IF/00268/2013/CP1173/CT0006) to MS, and by Grant GM54395 from the National Institutes of Health (www.nih.gov) to CPM. and GM081571 from the National Institutes of Health to PE.
• Research Categories: Biology, Cell; Biology, Genetics

Abstract

Gene expression during spore development in Bacillus subtilis is controlled by cell type-specific RNA polymerase sigma factors. σFand σE control early stages of development in the forespore and the mother cell, respectively. When, at an intermediate stage in development, the mother cell engulfs the forespore, σF is replaced by σG and σE is replaced by σK. The anti-sigma factor CsfB is produced under the control of σF and binds to and inhibits the auto-regulatory σG, but not σF. A position in region 2.1, occupied by an asparagine in σG and by a glutamate in οF, is sufficient for CsfB discrimination of the two sigmas, and allows it to delay the early to late switch in forespore gene expression. We now show that following engulfment completion, csfB is switched on in the mother cell under the control of σK and that CsfB binds to and inhibits σE but not σK, possibly to facilitate the switch from early to late gene expression. We show that a position in region 2.3 occupied by a conserved asparagine in σE and by a conserved glutamate in σK suffices for discrimination by CsfB. We also show that CsfB prevents activation of σG in the mother cell and the premature σG-dependent activation of σK. Thus, CsfB establishes negative feedback loops that curtail the activity of σE and prevent the ectopic activation of σG in the mother cell. The capacity of CsfB to directly block σE activity may also explain how CsfB plays a role as one of the several mechanisms that prevent σE activation in the forespore. Thus the capacity of CsfB to differentiate between the highly similar σF/σG and σE/σK pairs allows it to rinforce the cell-type specificity of these sigma factors and the transition from early to late development in B. subtilis, and possibly in all sporeformers that encode a CsfB orthologue.