Serrano Mónica, Gao JinXin, Bota João, Bate Ashley R, Meisner Jeffrey, Eichenberger Patrick, Moran Charles P, Henriques Adriano O
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Estação Agronómica Nacional, Oeiras, Portugal.
Emory University School of Medicine, Atlanta, Georgia, United States of America.
PLoS Genet. 2015 Apr 2;11(4):e1005104. doi: 10.1371/journal.pgen.1005104. eCollection 2015 Apr.
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.
枯草芽孢杆菌孢子发育过程中的基因表达受细胞类型特异性RNA聚合酶σ因子控制。σF和σE分别控制前芽孢和母细胞发育的早期阶段。在发育的中间阶段，当母细胞吞噬前芽孢时，σF被σG取代，σE被σK取代。抗σ因子CsfB在σF的控制下产生，它与自动调节的σG结合并抑制其活性，但不抑制σF。在区域2.1中的一个位置，σG中由天冬酰胺占据，σF中由谷氨酸占据，这足以使CsfB区分这两种σ因子，并使其能够延迟前芽孢基因表达从早期到晚期的转换。我们现在表明，在吞噬完成后，csfB在σK的控制下在母细胞中开启，并且CsfB与σE结合并抑制其活性，但不抑制σK，这可能有助于促进从早期到晚期基因表达的转换。我们表明，在区域2.3中的一个位置，σE中由保守的天冬酰胺占据，σK中由保守的谷氨酸占据，足以使CsfB进行区分。我们还表明，CsfB可防止母细胞中σG的激活以及σK依赖于σG的过早激活。因此，CsfB建立了负反馈回路，减少了σE的活性，并防止母细胞中σG的异位激活。CsfB直接阻断σE活性的能力也可以解释CsfB如何作为防止前芽孢中σE激活的几种机制之一发挥作用。因此，CsfB区分高度相似的σF/σG和σE/σK对的能力使其能够加强这些σ因子的细胞类型特异性以及枯草芽孢杆菌中从早期到晚期发育的转变，并且可能在所有编码CsfB直系同源物的芽孢形成菌中都如此。
