High- and low-affinity cre boxes for CcpA binding in Bacillus subtilis revealed by genome-wide analysis.
High- and low-affinity cre boxes for CcpA binding in Bacillus subtilis revealed by genome-wide analysis.
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DOI：
10.1186/1471-2164-13-401
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发表时间：
2012-08-17
期刊：
影响因子：
4.4
通讯作者：
Kuipers OP
中科院分区：
文献类型：
--
作者：
Marciniak BC;Pabijaniak M;de Jong A;Dűhring R;Seidel G;Hillen W;Kuipers OP
在枯草芽孢杆菌及其近亲碳分解代谢物控制中，一种能够达到碳和能源代谢最大效率的机制是通过全局调节器 CcpA（碳分解代谢物蛋白 A）实现的。 CcpA 与 HPr-Ser-P（含组氨酸蛋白的丝氨酰磷酸化形式，HPr）形成复合物，与称为分解代谢物响应元件 cre 的操纵位点结合。根据 cre 盒相对于启动子的位置，CcpA/HPr-Ser-P 复合物可以充当正调节剂或负调节剂。 cre 盒是高度简并的半回文，具有低保守性的共有序列。到目前为止，旨在揭示 CcpA 如何结合如此多样化位点的研究主要集中在单个 cre 盒的分析上。在这项研究中，对cre位点进行了全基因组分析，以确定cre序列和位置的差异，这决定了它们的结合亲和力。比较了具有三种不同 CcpA 表达水平的枯草芽孢杆菌培养物的转录组。细胞中 CcpA 的量越高，拥有 cre 位点的操纵子就越多，受到差异调节。在低 CcpA 水平下介导调节的 cre 盒被指定为强（高亲和力），而那些仅对大量 CcpA 做出反应的则被指定为弱（低亲和力）。揭示了强cre盒和弱cre盒之间与转录起始位点相关的序列和位置的差异。 cre 盒中特定位置的某些残基以及在一定程度上 cre 序列的回文性质和 cre 紧邻转录起始位点的位置有助于 CcpA 依赖性调节的强度。确定了影响 cre 调节效率的主要因素，从而能够对 CcpA 调节子的各个子调节子进行微妙的差异控制。
In Bacillus subtilis and its relatives carbon catabolite control, a mechanism enabling to reach maximal efficiency of carbon and energy sources metabolism, is achieved by the global regulator CcpA (carbon catabolite protein A). CcpA in a complex with HPr-Ser-P (seryl-phosphorylated form of histidine-containing protein, HPr) binds to operator sites called catabolite responsive elements, cre. Depending on the cre box position relative to the promoter, the CcpA/HPr-Ser-P complex can either act as a positive or a negative regulator. The cre boxes are highly degenerate semi-palindromes with a lowly conserved consensus sequence. So far, studies aimed at revealing how CcpA can bind such diverse sites were focused on the analysis of single cre boxes. In this study, a genome-wide analysis of cre sites was performed in order to identify differences in cre sequence and position, which determine their binding affinity. The transcriptomes of B. subtilis cultures with three different CcpA expression levels were compared. The higher the amount of CcpA in the cells, the more operons possessing cre sites were differentially regulated. The cre boxes that mediated regulation at low CcpA levels were designated as strong (high affinity) and those which responded only to high amounts of CcpA, as weak (low affinity). Differences in the sequence and position in relation to the transcription start site between strong and weak cre boxes were revealed. Certain residues at specific positions in the cre box as well as, to a certain extent, a more palindromic nature of cre sequences and the location of cre in close vicinity to the transcription start site contribute to the strength of CcpA-dependent regulation. The main factors contributing to cre regulatory efficiencies, enabling subtle differential control of various subregulons of the CcpA regulon, are identified.
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影响因子：
4.4
作者：
de Jong A;Pietersma H;Cordes M;Kuipers OP;Kok J
通讯作者：
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影响因子：
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作者：
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