title: Inducible nitric oxide synthase (iNOS) regulatory region variation in non-human primates.
abstract: Inducible nitric oxide synthase (iNOS) is an enzyme that plays a key role in intracellular immune response against respiratory infections. Since various species of nonhuman primates exhibit different levels of susceptibility to infectious respiratory diseases, and since variation in regulatory regions of genes is thought to play a key role in expression levels of genes, two candidate regulatory regions of iNOS were mapped, sequenced, and compared across five species of nonhuman primates: African green monkeys (Chlorocebus sabaeus), pig-tailed macaques (Macaca nemestrina), cynomolgus macaques (Macaca fascicularis), Indian rhesus macaques (Macaca mulatta), and Chinese rhesus macaques (M. mulatta). In addition, we conducted an in silico analysis of the transcription factor binding sites associated with genetic variation in these two candidate regulatory regions across species. We found that only one of the two candidate regions showed strong evidence of involvement in iNOS regulation. Specifically, we found evidence of 13 conserved binding site candidates linked to iNOS regulation: AP-1, C/EBPB, CREB, GATA-1, GATA-3, NF-AT, NF-AT5, NF-κB, KLF4, Oct-1, PEA3, SMAD3, and TCF11. Additionally, we found evidence of interspecies variation in binding sites for several regulatory elements linked to iNOS (GATA-3, GATA-4, KLF6, SRF, STAT-1, STAT-3, OLF-1 and HIF-1) across species, especially in African green monkeys relative to other species. Given the key role of iNOS in respiratory immune response, the findings of this study might help guide the direction of future studies aimed to uncover the molecular mechanisms underlying the increased susceptibility of African green monkeys to several viral and bacterial respiratory infections.
authors: Graduate Group of Comparative Pathology, School of Veterinary Medicine, University of California, Davis, United States; Molecular Anthropology Laboratory, Department of Anthropology, University of California, Davis, United States; California National Primate Research Center (CNPRC), University of California, Davis, United States. Electronic address: mroodgar@ucdavis.edu.
authors: Morteza
authors: M
authors: Roodgar
authors: Molecular Anthropology Laboratory, Department of Anthropology, University of California, Davis, United States; Santa Fe Institute, Santa Fe, NM, United States. Electronic address: ctross@ucdavis.edu.
authors: Cody T
authors: CT
authors: Ross
authors: Department of Internal Medicine, Division of Pulmonary and Critical Care, School of Medicine, University of California, Davis, United States.
authors: Nicholas J
authors: NJ
authors: Kenyon
authors: Molecular Anthropology Laboratory, Department of Anthropology, University of California, Davis, United States.
authors: Gretchen
authors: G
authors: Marcelino
authors: Graduate Group of Comparative Pathology, School of Veterinary Medicine, University of California, Davis, United States; Molecular Anthropology Laboratory, Department of Anthropology, University of California, Davis, United States; California National Primate Research Center (CNPRC), University of California, Davis, United States.
authors: David Glenn
authors: DG
authors: Smith
mesh_terms: D000818:Animals; D001665:Binding Sites; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D014644:Genetic Variation; D000090062:Kruppel-Like Factor 4; D008253:Macaca mulatta; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors; D052247:Nitric Oxide Synthase Type II
keywords: Immune response; Non-human primates; Regulatory region; iNOS