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Identification of Hookworm DAF-16/FOXO Response Elements and Direct Gene Targets

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 transcrip...

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Autores principales: Gao, Xin, Wang, Zhengyuan, Martin, John, Abubucker, Sahar, Zhang, Xu, Mitreva, Makedonka, Hawdon, John M.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924398/
https://www.ncbi.nlm.nih.gov/pubmed/20808816
http://dx.doi.org/10.1371/journal.pone.0012289
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author Gao, Xin
Wang, Zhengyuan
Martin, John
Abubucker, Sahar
Zhang, Xu
Mitreva, Makedonka
Hawdon, John M.
author_facet Gao, Xin
Wang, Zhengyuan
Martin, John
Abubucker, Sahar
Zhang, Xu
Mitreva, Makedonka
Hawdon, John M.
author_sort Gao, Xin
collection PubMed
description 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 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.
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spelling pubmed-29243982010-08-31 Identification of Hookworm DAF-16/FOXO Response Elements and Direct Gene Targets Gao, Xin Wang, Zhengyuan Martin, John Abubucker, Sahar Zhang, Xu Mitreva, Makedonka Hawdon, John M. PLoS One Research Article 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 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. Public Library of Science 2010-08-19 /pmc/articles/PMC2924398/ /pubmed/20808816 http://dx.doi.org/10.1371/journal.pone.0012289 Text en Gao et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gao, Xin
Wang, Zhengyuan
Martin, John
Abubucker, Sahar
Zhang, Xu
Mitreva, Makedonka
Hawdon, John M.
Identification of Hookworm DAF-16/FOXO Response Elements and Direct Gene Targets
title Identification of Hookworm DAF-16/FOXO Response Elements and Direct Gene Targets
title_full Identification of Hookworm DAF-16/FOXO Response Elements and Direct Gene Targets
title_fullStr Identification of Hookworm DAF-16/FOXO Response Elements and Direct Gene Targets
title_full_unstemmed Identification of Hookworm DAF-16/FOXO Response Elements and Direct Gene Targets
title_short Identification of Hookworm DAF-16/FOXO Response Elements and Direct Gene Targets
title_sort identification of hookworm daf-16/foxo response elements and direct gene targets
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924398/
https://www.ncbi.nlm.nih.gov/pubmed/20808816
http://dx.doi.org/10.1371/journal.pone.0012289
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