Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite.
Identification and genome-wide prediction of DNA binding specificities for the ApiAP2 family of regulators from the malaria parasite.
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DOI：
10.1371/journal.ppat.1001165
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发表时间：
2010-10-28
期刊：
影响因子：
6.7
通讯作者：
Llinás M
中科院分区：
文献类型：
--
作者：
Campbell TL;De Silva EK;Olszewski KL;Elemento O;Llinás M
顶复门寄生虫转录调控的分子机制仍然知之甚少。最近，顶复门AP2（ApiAP2）DNA结合蛋白家族被鉴定为在所有顶复门中发现的主要类别的转录调节因子。为了深入了解这些蛋白质在疟原虫中的调节作用，我们全面调查了来自恶性疟原虫的ApiAP 2蛋白家族的所有27个成员的DNA结合特异性，揭示了大多数这些DNA结合蛋白的独特结合偏好。除了高亲和力的初级基序相互作用，我们还观察到与次级基序的相互作用。许多ApiAP2蛋白结合多个不同基序的能力显著增加了由ApiAP2家族控制的转录调控网络的潜在复杂性。使用这些新发现的序列基序，我们推断与先前报道的疟原虫顺式元件相关的反式因子，并提供证据表明ApiAP2蛋白在寄生虫发育的所有阶段调节关键的调控决定。我们的研究结果提供了ApiAP 2 DNA结合特异性的详细视图，并为推断恶性疟原虫的全面基因调控网络迈出了第一步。 恶性疟原虫是造成人类毁灭性疾病疟疾的主要原因。这种寄生生物具有复杂的生命周期，跨越蚊子载体和人类宿主中的各种不同细胞类型。为了适应这些不同的环境并在其中生存，寄生虫在其整个生命周期中精确地调节基因的转录。然而，恶性疟原虫的转录调控机制知之甚少。迄今为止，已经鉴定了一个特异性转录因子家族，即顶复门AP2（ApiAP2）蛋白。这些DNA结合蛋白可能在协调这种寄生虫的发展中发挥重要作用，因此具有重大意义。在这里，我们确定了整个恶性疟原虫ApiAP2家族DNA结合蛋白的DNA结合特异性。我们的研究结果表明，这些蛋白质结合不同的DNA序列基序和共同出现在功能相关的基因组。通过绘制寄生虫基因组中的这些序列，我们可以开始建立寄生虫发育的调控网络。这项研究代表了恶性疟原虫中DNA结合蛋白家族的第一个特征，并为了解这种寄生虫的基因调控迈出了重要的一步。
The molecular mechanisms underlying transcriptional regulation in apicomplexan parasites remain poorly understood. Recently, the Apicomplexan AP2 (ApiAP2) family of DNA binding proteins was identified as a major class of transcriptional regulators that are found across all Apicomplexa. To gain insight into the regulatory role of these proteins in the malaria parasite, we have comprehensively surveyed the DNA-binding specificities of all 27 members of the ApiAP2 protein family from Plasmodium falciparum revealing unique binding preferences for the majority of these DNA binding proteins. In addition to high affinity primary motif interactions, we also observe interactions with secondary motifs. The ability of a number of ApiAP2 proteins to bind multiple, distinct motifs significantly increases the potential complexity of the transcriptional regulatory networks governed by the ApiAP2 family. Using these newly identified sequence motifs, we infer the trans-factors associated with previously reported plasmodial cis-elements and provide evidence that ApiAP2 proteins modulate key regulatory decisions at all stages of parasite development. Our results offer a detailed view of ApiAP2 DNA binding specificity and take the first step toward inferring comprehensive gene regulatory networks for P. falciparum. Plasmodium falciparum is the main cause of the devastating human disease malaria. This parasitic organism has a complex lifecycle spanning a variety of different cell types in the mosquito vector and human host. To adapt and survive in these different environments, the parasite precisely regulates the transcription of genes throughout its lifecycle. However, the mechanisms governing transcriptional regulation in P. falciparum are poorly understood. To date, a single family of specific transcription factors, the Apicomplexan AP2 (ApiAP2) proteins, has been identified. These DNA binding proteins are likely to play a major role in coordinating the development of this parasite and are therefore of major interest. Here, we determine the DNA binding specificities for the entire P. falciparum ApiAP2 family of DNA binding proteins. Our results demonstrate that these proteins bind diverse DNA sequence motifs and co-occur in functionally related sets of genes. By mapping these sequences throughout the parasite genome, we can begin to establish a regulatory network underlying parasite development. This study represents the first characterization of a family of DNA binding proteins in P. falciparum and provides an important step towards understanding gene regulation in this parasite.
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影响因子：
14.9
作者：
Cole C;Barber JD;Barton GJ
通讯作者：
Barton GJ
影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
4.4
作者：
Callebaut, I;Prat, K;Meurice, E;Mornon, JP;Tomavo, S
通讯作者：
Tomavo, S
影响因子：
14.8
作者：
Berger, Michael F.;Bulyk, Martha L.
通讯作者：
Bulyk, Martha L.
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML