Often in development, cells resort to positive feedback loops to steadily and robustly increase the concentration of transcription factors that in turn activate a particular developmental path. Efficient as it may be, this positive auto-regulation raises the question of how to prevent a positive feedback loop from being activated when it is not appropriate for the cells. Researchers fromthe Microbial Development Lab have uncovered a negative feedback loop that tightly controls a positive feedback loop necessary for bacterial sporulation in the non-sporulating cells. Results are published in Plos Genetics.
In unfavorable conditions, rod-shaped bacteria like Bacillus subtilis undergo an asymmetric division and a resistant spore is formed inside the larger (mother) cell. This endosporulation process is tightly controlled by a number of transcription factors. In particular, sigma G is activated in the forespore (one of the two chambers of the developing cell) at an intermediate stage in spore development. Once active, a positive feedback loop allows the rapid accumulation of sigma G, and the robust expression of a large number of genes. The study of the ITQB team now shows that activation of this positive feedback loop is prevented in non-sporulating (vegetative) cells, through the sigma G-dependent production of an anti-sigma factor (CsfB). The negative feedback loop thus established, effectively counteracts the positive loop involving sigma G, thereby limiting the ectopic (i.e, in non-sporulating cells) activation of the sigma factor.
Interestingly, the sigma / anti-sigma interaction is dependent on a single specific aminoacid. The study also identifies an asparagine residue critical for binding and inhibition of sigma G by CsfB, whose substitution is sufficient to confer immunity to the anti-sigma factor.
Short title: Avoiding the ectopic activity of a sigma factor
PLoS Genet 7(9): e1002220. doi:10.1371/journal.pgen.1002220
A Negative Feedback Loop that Limits the Ectopic Activation of a Cell Type-Specific Sporulation Sigma Factor of Bacillus subtilis
Mónica Serrano1, Gonçalo Real1,†, Joana Santos1,#,†, Jorge Carneiro2, Charles P. Moran Jr. 3, and Adriano O. Henriques1*
1) Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Avenida da República, Apartado 127, 2781-901 Oeiras Codex, Portugal; 2) Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2781-901 Oeiras, Portugal; 3) Emory University School of Medicine, Department of Microbiology and Immunology, Atlanta GA 30322, U.S.A.