A generic approach to identify Transcription Factor-specific operator motifs; Inferences for LacI-family mediated regulation in Lactobacillus plantarum WCFS1.
A generic approach to identify Transcription Factor-specific operator motifs; Inferences for LacI-family mediated regulation in Lactobacillus plantarum WCFS1.
复制标题
DOI：
10.1186/1471-2164-9-145
复制
发表时间：
2008-03-27
期刊：
影响因子：
4.4
通讯作者：
Siezen RJ
中科院分区：
文献类型：
--
作者：
Francke C;Kerkhoven R;Wels M;Siezen RJ
基于序列重建细菌调控网络的一个关键问题是操作员预测缺乏特异性。该问题在转录因子（TF）特异性结合位点的鉴定中尤为突出。更特别的是，同源转录因子非常丰富，并且由于它们在结构上非常相似，因此很难通过自动化手段区分相关的运算符。这也适用于 LacI 家族，这是一个经过充分研究的 TF 家族，其许多成员在控制细菌碳水化合物分解代谢（包括分解代谢物抑制）方面发挥着关键作用。为了克服特异性问题，制定了一种全面的足迹方法来识别 TF 特异性操纵子基序，并将其应用于模型革兰氏阳性生物体植物乳杆菌 WCFS1 中的 LacI 家族 TF。该方法背后的主要前提是，只有共享直系同源基因组背景的直系同源序列才会共享等效的调控位点。当该方法应用于模型物种的 12 个 LacI 家族转录因子时，为每个转录因子识别了一个特定的操纵子基序。通过 TF 特异性操纵子基序，在基因组上发现了潜在的结合位点，并且可以定义推定的最小调节子。此外，在大多数情况下，特定诱导子可以通过系统发育与转录因子联系起来，从而揭示这些调节子的生物学作用。算子预测表明 LacI 家族 TF 可以分为两个具有明显不同算子基序的亚家族。他们还确定，与“全局”调节器 CcpA 相关的操作符本质上与其他 LacI 家族成员的操作符并无区别，只是更加简并。对已识别的推定结合位点的染色体位置的分析证实，LacI 家族转录因子大多是自动调节的，主要与碳水化合物的摄取和分解代谢有关。我们为不同 TF 家族成员识别特定操作基序的方法是特定的，但本质上是通用的。数据推断，虽然特定操纵子基序可用于识别最小调节子，但关于 TF 活性的实验知识对于确定完整调节子以及估计 TF 亲和力之间的重叠尤其重要。
A key problem in the sequence-based reconstruction of regulatory networks in bacteria is the lack of specificity in operator predictions. The problem is especially prominent in the identification of transcription factor (TF) specific binding sites. More in particular, homologous TFs are abundant and, as they are structurally very similar, it proves difficult to distinguish the related operators by automated means. This also holds for the LacI-family, a family of TFs that is well-studied and has many members that fulfill crucial roles in the control of carbohydrate catabolism in bacteria including catabolite repression. To overcome the specificity problem, a comprehensive footprinting approach was formulated to identify TF-specific operator motifs and was applied to the LacI-family of TFs in the model gram positive organism, Lactobacillus plantarum WCFS1. The main premise behind the approach is that only orthologous sequences that share orthologous genomic context will share equivalent regulatory sites. When the approach was applied to the 12 LacI-family TFs of the model species, a specific operator motif was identified for each of them. With the TF-specific operator motifs, potential binding sites were found on the genome and putative minimal regulons could be defined. Moreover, specific inducers could in most cases be linked to the TFs through phylogeny, thereby unveiling the biological role of these regulons. The operator predictions indicated that the LacI-family TFs can be separated into two subfamilies with clearly distinct operator motifs. They also established that the operator related to the 'global' regulator CcpA is not inherently distinct from that of other LacI-family members, only more degenerate. Analysis of the chromosomal position of the identified putative binding sites confirmed that the LacI-family TFs are mostly auto-regulatory and relate mainly to carbohydrate uptake and catabolism. Our approach to identify specific operator motifs for different TF-family members is specific and in essence generic. The data infer that, although the specific operator motifs can be used to identify minimal regulons, experimental knowledge on TF activity especially is essential to determine complete regulons as well as to estimate the overlap between TF affinities.
登录
查看更多内容
Pfam：氏族、网络工具和服务。
影响因子：
14.9
作者：
Finn, Robert D.;Mistry, Jaina;Schuster-Bockler, Benjamin;Griffiths-Jones, Sam;Hollich, Volker;Lassmann, Timo;Moxon, Simon;Marshall, Mhairi;Khanna, Ajay;Durbin, Richard;Eddy, Sean R.;Sonnhammer, Erik L. L.;Bateman, Alex
通讯作者：
Bateman, Alex
影响因子：
64.8
作者：
Becskei, A;Serrano, L
通讯作者：
Serrano, L
影响因子：
5.6
作者：
Babu, MM;Teichmann, SA;Aravind, L
通讯作者：
Aravind, L
影响因子：
4.2
作者：
Andersson U;Rådström P
通讯作者：
Rådström P
影响因子：
3.2
作者：
Daniel, RA;Haiech, J;Errington, J
通讯作者：
Errington, J