Identification of hookworm DAF-16/FOXO response elements and direct gene targets

Xin Gao, Zhengyuan Wang, John Martin, Sahar Abubucker, Xu Zhang, Makedonka Mitreva, John M. Hawdon

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Background: 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. Methodology/Principal Findings: 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 stagespecific expression patterns were examined. Also, a new putative DAF-16 binding element was identified. Conclusions/Significance: 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.

Original languageEnglish
Article numbere12289
JournalPloS one
Issue number8
StatePublished - Oct 20 2010

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    Gao, X., Wang, Z., Martin, J., Abubucker, S., Zhang, X., Mitreva, M., & Hawdon, J. M. (2010). Identification of hookworm DAF-16/FOXO response elements and direct gene targets. PloS one, 5(8), [e12289].