Identification of hookworm DAF-16/FOXO response elements and direct gene targets.
Identification of hookworm DAF-16/FOXO response elements and direct gene targets.
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DOI：
10.1371/journal.pone.0012289
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发表时间：
2010-08-19
期刊：
影响因子：
3.7
通讯作者：
Hawdon JM
中科院分区：
文献类型：
--
作者：
Gao X;Wang Z;Martin J;Abubucker S;Zhang X;Mitreva M;Hawdon JM
寄生线虫钩虫的感染阶段在环境中发育停滞，需要感染特定的宿主才能完成其生命周期。犬钩虫（Ancylostoma caninum）是研究人类钩虫感染的极好模型。A.犬钩虫（Ac-heparin-16）具有特征性的叉头或“翼螺旋”DNA结合结构域（DBD），其与钩虫在宿主中发育的恢复有关。然而，Ac-Arg-16在钩虫寄生及其下游靶点中的确切作用尚不清楚。在本研究中，我们结合分子生物学技术和生物信息学来确定一组Ac-Arg-16结合位点和靶基因。使用Ac-Arg-16的DNA结合结构域通过体外基因组选择来选择基因组片段。分析了24个结合的基因组片段中是否存在Ac-p16家族结合元件（DBE）和可能的替代Ac-p16结合基序。使用生物信息学工具鉴定了与这些基因组片段相关的22个基因，并将其定义为Ac-Arg-16的候选直接基因靶标。它们的发育阶段特异性的表达模式进行了检查。此外，一个新的推定的β-16结合元件被确定。我们的研究结果表明，Ac-BRA-16是参与不同的生物学过程，在整个钩虫的发展。对这些靶基因的进一步研究将有助于深入了解Ac-B16在钩虫感染中调控其下游基因网络的分子基础。
The infective stage of the parasitic nematode hookworm is developmentally arrested in the environment and needs to infect a specific host to complete its life cycle. The canine hookworm (Ancylostoma caninum) is an excellent model for investigating human hookworm infections. The transcription factor of A. caninum, Ac-DAF-16, which has a characteristic fork head or “winged helix” DNA binding domain (DBD), has been implicated in the resumption of hookworm development in the host. However, the precise roles of Ac-DAF-16 in hookworm parasitism and its downstream targets are unknown. In the present study, we combined molecular techniques and bioinformatics to identify a group of Ac-DAF-16 binding sites and target genes. The DNA binding domain of Ac-DAF-16 was used to select genomic fragments by in vitro genomic selection. Twenty four bound genomic fragments were analyzed for the presence of the DAF-16 family binding element (DBE) and possible alternative Ac-DAF-16 bind motifs. The 22 genes linked to these genomic fragments were identified using bioinformatics tools and defined as candidate direct gene targets of Ac-DAF-16. Their developmental stage-specific expression patterns were examined. Also, a new putative DAF-16 binding element was identified. Our results show that Ac-DAF-16 is involved in diverse biological processes throughout hookworm development. Further investigation of these target genes will provide insights into the molecular basis by which Ac-DAF-16 regulates its downstream gene network in hookworm infection.
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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
影响因子：
4
作者：
Hu M;Lok JB;Ranjit N;Massey HC Jr;Sternberg PW;Gasser RB
通讯作者：
Gasser RB
DOI：
10.1073/pnas.89.18.8754
发表时间：
1992-09-15
影响因子：
11.1
作者：
HACKER, U;GROSSNIKLAUS, U;JACKLE, H
通讯作者：
JACKLE, H
影响因子：
1.5
作者：
Abubucker, Sahar;Martin, John;Mitreva, Makedonka
通讯作者：
Mitreva, Makedonka
影响因子：
4
作者：
Brand, A;Hawdon, JM
通讯作者：
Hawdon, JM