title: Identification of hookworm DAF-16/FOXO response elements and direct gene targets.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Microbiology and Tropical Medicine, The George Washington University Medical Center, Washington, District of Columbia, United States of America.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Martin
authors.forename: Sahar
authors.initials: S
authors.lastname: Abubucker
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Makedonka
authors.initials: M
authors.lastname: Mitreva
authors.forename: John M
authors.initials: JM
authors.lastname: Hawdon
mesh_terms: D000595:Amino Acid Sequence; D000723:Ancylostomatoidea / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D017238:Genes, Helminth / Q000235:genetics*; D023281:Genomics; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D020218:Response Elements / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D008024:Ligands; D004247:DNA
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