Differential control of Bradyrhizobium japonicum iron stimulon genes through variable affinity of the iron response regulator (Irr) for target gene promoters and selective loss of activator function.
Differential control of Bradyrhizobium japonicum iron stimulon genes through variable affinity of the iron response regulator (Irr) for target gene promoters and selective loss of activator function.
复制标题
通过铁反应调节剂 (Irr) 对靶基因启动子的可变亲和力和激活子功能的选择性丧失来差异控制日本慢生根瘤菌铁刺激基因。
DOI：
10.1111/mmi.12584
复制
发表时间：
2014
影响因子：
3.6
通讯作者：
O'Brian,MarkR
中科院分区：
文献类型：
--
作者：
Jaggavarapu,Siddharth;O'Brian,MarkR
Bradyrhizobium japonicumIrr 是一种条件稳定的转录激活剂和阻遏物，在铁限制、锰充足的条件下在细胞中积累，但在高铁条件、锰限制或暴露于 H2O2 时以血红素依赖性方式降解。在这里，我们鉴定了 Irr 调节基因，这些基因对促进 Irr 降解的因素相对无反应。这些基因的启动子与 Irr 的结合亲和力至少比响应基因的启动子高 200 倍，从而在较宽的细胞 Irr 浓度范围内维持启动子占据。对于 Irr 抑制基因，启动子占据与转录抑制相关，导致基于 Irr 对目标启动子的亲和力而产生不同的表达水平。然而，正控基因的失活既不需要启动子空位，也不需要 Irr 丧失 DNA 结合活性。因此，Irr 的激活和抑制功能在某些条件下可能彼此分离。 Irr 激活功能的消除是血红素依赖性的，因此血红素在调节 Irr 活性方面具有两个功能上可分离的作用。研究结果表明，Irr 的控制比单独通过条件稳定性实现的控制更为复杂。我们认为这些调节机制适应了 Irr 调节子基因的不同需求，以响应细胞的普遍代谢状态。
Bradyrhizobium japonicumIrr is a conditionally stable transcriptional activator and repressor that accumulates in cells under iron‐limited, manganese‐replete conditions, but degrades in a haem‐dependent manner under high iron conditions, manganese limitation or upon exposure to H2O2. Here, we identified Irr‐regulated genes that were relatively unresponsive to factors that promote Irr degradation. The promoters of those genes bound Irr with at least 200‐fold greater affinity than promoters of the responsive genes, resulting in maintenance of promoter occupancy over a wide cellular Irr concentration range. For Irr‐repressible genes, promoter occupancy correlated with transcriptional repression, resulting in differential levels of expression based on Irr affinity for target promoters. However, inactivation of positively controlled genes required neither promoter vacancy nor loss of DNA‐binding activity by Irr. Thus, activation and repression functions of Irr may be uncoupled from each other under certain conditions. Abrogation of Irr activation function was haem‐dependent, thus haem has two functionally separable roles in modulating Irr activity. The findings imply a greater complexity of control by Irr than can be achieved by conditional stability alone. We suggest that these regulatory mechanisms accommodate the differing needs for Irr regulon genes in response to the prevailing metabolic state of the cell.