Response regulator heterodimer formation controls a key stage in Streptomyces development.
Response regulator heterodimer formation controls a key stage in Streptomyces development.
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DOI：
10.1371/journal.pgen.1004554
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发表时间：
2014-08
期刊：
影响因子：
4.5
通讯作者：
Buttner MJ
中科院分区：
文献类型：
--
作者：
Al-Bassam MM;Bibb MJ;Bush MJ;Chandra G;Buttner MJ
孤儿，非典型反应调节BldM和WhiI在链霉菌分化中发挥关键作用。BldM是形成气生菌丝所必需的，而WhiI是这些生殖结构分化成成熟孢子所必需的。为了深入了解BldM功能，我们使用ChIP-Seq和转录谱分析来定义全基因组BldM调节子。BldM靶基因基于它们的whi基因依赖性聚类成两组。第I组基因的表达依赖于bldM，但独立于所有的whi基因，和生化实验表明，第I组启动子控制的BldM同源二聚体。相反，II组基因的表达晚于I组基因，它们的表达不仅依赖于bldM，还依赖于whiI和whiG（编码激活whiI的sigma因子）。另外的ChIP-Seq分析表明，BldM组II基因也是WhiI的直接靶点，并且WhiI与这些启动子的体内结合依赖于BldM，反之亦然。我们继续证明，BldM和WhiI形成一个功能异源二聚体，控制组II启动子，服务于整合来自两个不同的发展途径的信号。因此，BldM-WhiI系统证实了反应调节剂异二聚体形成作为扩大细菌细胞信号传导能力的机制的潜力。双组分信号转导系统是调控细菌基因表达的主要手段。因此，认识到与这些系统相关的机制的多样性对于理解细菌细胞的全部信号传导潜力至关重要。我们分析了两个孤儿的行为，非典型的反应调节器，在控制丝状细菌链霉菌BldM和WhiI的形态分化中发挥关键作用。我们证明，BlDM激活其第一组目标启动子作为一个同源二聚体，但它随后激活其第二组目标启动子通过形成一个功能异源二聚体与WhiI。因此，BldM-WhiI异二聚体的形成代表了一种不寻常的机制，用于靶基因的共激活和启动子处的调节信号的整合，增强了与双组分系统相关的已知的信号传导能力。
The orphan, atypical response regulators BldM and WhiI each play critical roles in Streptomyces differentiation. BldM is required for the formation of aerial hyphae, and WhiI is required for the differentiation of these reproductive structures into mature spores. To gain insight into BldM function, we defined the genome-wide BldM regulon using ChIP-Seq and transcriptional profiling. BldM target genes clustered into two groups based on their whi gene dependency. Expression of Group I genes depended on bldM but was independent of all the whi genes, and biochemical experiments showed that Group I promoters were controlled by a BldM homodimer. In contrast, Group II genes were expressed later than Group I genes and their expression depended not only on bldM but also on whiI and whiG (encoding the sigma factor that activates whiI). Additional ChIP-Seq analysis showed that BldM Group II genes were also direct targets of WhiI and that in vivo binding of WhiI to these promoters depended on BldM and vice versa. We go on to demonstrate that BldM and WhiI form a functional heterodimer that controls Group II promoters, serving to integrate signals from two distinct developmental pathways. The BldM-WhiI system thus exemplifies the potential of response regulator heterodimer formation as a mechanism to expand the signaling capabilities of bacterial cells. Two-component signal transduction systems are a primary means of regulating gene expression in bacteria. Recognizing the diversity of mechanisms associated with these systems is therefore critical to understanding the full signaling potential of bacterial cells. We have analyzed the behavior of two orphan, atypical response regulators that play key roles in controlling morphological differentiation in the filamentous bacteria Streptomyces-BldM and WhiI. We demonstrate that BldM activates its Group I target promoters as a homodimer, but that it subsequently activates its Group II target promoters by forming a functional heterodimer with WhiI. BldM-WhiI heterodimer formation thus represents an unusual mechanism for the coactivation of target genes and the integration of regulatory signals at promoters, enhancing the known repertoire of signaling capabilities associated with two-component systems.
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影响因子：
3.6
作者：
Fraser JS;Merlie JP Jr;Echols N;Weisfield SR;Mignot T;Wemmer DE;Zusman DR;Alber T
通讯作者：
Alber T
影响因子：
6.4
作者：
Bush MJ;Bibb MJ;Chandra G;Findlay KC;Buttner MJ
通讯作者：
Buttner MJ
影响因子：
3.2
作者：
Bibb, MJ;Molle, V;Buttner, MJ
通讯作者：
Buttner, MJ
影响因子：
3.6
作者：
Claessen, D;Stokroos, I;Wösten, HAB
通讯作者：
Wösten, HAB
DOI：
10.1073/pnas.0337542100
发表时间：
2003-02-18
影响因子：
11.1
作者：
Gust, B;Challis, GL;Chater, KF
通讯作者：
Chater, KF