Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile.
Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile.
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DOI：
10.1093/nar/gks864
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发表时间：
2012-11
影响因子：
14.9
通讯作者：
Dupuy B
中科院分区：
文献类型：
--
作者：
Antunes A;Camiade E;Monot M;Courtois E;Barbut F;Sernova NV;Rodionov DA;Martin-Verstraete I;Dupuy B
在革兰氏阳性细菌中，分解代谢控制蛋白CcpA是一种多向调节因子，介导对快速分解代谢碳水化合物（如葡萄糖）的全球转录反应。通过全转录组分析，我们表征了艰难梭菌中葡萄糖依赖和ccpa依赖的基因调控。艰难梭菌基因中约18%受葡萄糖调控，其中50%依赖CcpA进行调控。CcpA调控子包括参与糖摄取、发酵和氨基酸代谢的基因，证实了CcpA作为碳氮途径之间的纽带的作用。结合染色质免疫沉淀和基因组序列分析，我们检测到55个CcpA结合位点，对应于CcpA直接控制的约140个基因。我们定义了艰难梭菌CcpA共识结合位点（creCD基序），即“RRGAAAANGTTTTCWW”。电泳迁移位移试验证实纯化的CcpA蛋白与19个creCD靶位点结合。CcpA还直接抑制孢子形成早期的关键因子（Spo0A和SigF）。此外，艰难梭菌毒素基因（tcdA和tcdB）及其调控因子（tcdR和tcdC）是CcpA的直接靶点。最后，CcpA通过调节一大批监管者来控制一个复杂而扩展的监管网络。
The catabolite control protein CcpA is a pleiotropic regulator that mediates the global transcriptional response to rapidly catabolizable carbohydrates, like glucose in Gram-positive bacteria. By whole transcriptome analyses, we characterized glucose-dependent and CcpA-dependent gene regulation in Clostridium difficile. About 18% of all C. difficile genes are regulated by glucose, for which 50% depend on CcpA for regulation. The CcpA regulon comprises genes involved in sugar uptake, fermentation and amino acids metabolism, confirming the role of CcpA as a link between carbon and nitrogen pathways. Using combination of chromatin immunoprecipitation and genome sequence analysis, we detected 55 CcpA binding sites corresponding to ∼140 genes directly controlled by CcpA. We defined the C. difficile CcpA consensus binding site (creCD motif), that is, ‘RRGAAAANGTTTTCWW’. Binding of purified CcpA protein to 19 target creCD sites was demonstrated by electrophoretic mobility shift assay. CcpA also directly represses key factors in early steps of sporulation (Spo0A and SigF). Furthermore, the C. difficile toxin genes (tcdA and tcdB) and their regulators (tcdR and tcdC) are direct CcpA targets. Finally, CcpA controls a complex and extended regulatory network through the modulation of a large set of regulators.
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影响因子：
4.4
作者：
Fonknechten N;Chaussonnerie S;Tricot S;Lajus A;Andreesen JR;Perchat N;Pelletier E;Gouyvenoux M;Barbe V;Salanoubat M;Le Paslier D;Weissenbach J;Cohen GN;Kreimeyer A
通讯作者：
Kreimeyer A
影响因子：
3.1
作者：
Karlsson, S;Lindberg, A;Åkerlund, T
通讯作者：
Åkerlund, T
影响因子：
3.2
作者：
Jackson, Sarah;Calos, Mary;Self, William T.
通讯作者：
Self, William T.
影响因子：
64.8
作者：
JUST, I;SELZER, J;AKTORIES, K
通讯作者：
AKTORIES, K
影响因子：
3
作者：
Emerson, Jenny E.;Stabler, Richard A.;Fairweather, Neil F.
通讯作者：
Fairweather, Neil F.