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

Gao, Xin and Wang, Zhengyuan and Martin, John and Abubucker, Sahar and Zhang, Ziping and Mitreva, Makedonka and Hawdon, John (2010) Identification of hookworm DAF-16/FOXO response elements and direct gene targets. PLoS One, 5 (8). e12289.

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Abstract

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/PrincipalFindings: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.
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.

Item Type: Article
Subjects: Medical and Health Sciences > Basic medicine
Divisions: Faculty of Medical Science
Depositing User: Mirjana Kocaleva
Date Deposited: 30 Nov 2012 15:23
Last Modified: 30 Nov 2012 15:23
URI: https://eprints.ugd.edu.mk/id/eprint/2679

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