title: Identification of FOXO targets that generate diverse features of the diapause phenotype in the mosquito Culex pipiens.
abstract: Insulin and juvenile hormone signaling direct entry of the mosquito Culex pipiens into its overwintering adult diapause, and these two critical signaling pathways appear to do so by converging on the regulation of forkhead transcription factor (FOXO). Diapause is a complex phenotype, and FOXO emerges as a prime candidate for activating many of the diverse physiological pathways that generate the diapause phenotype. Here, we used ChIP sequencing to identify direct targets of FOXO. The nearest gene in a 10-kb region surrounding a predicted binding site was extracted for each binding site, resulting in a dataset containing genes potentially regulated by FOXO. By selecting candidate genes based on their functional relevance to diapause, we identified five gene categories of potential interest, including stress tolerance, metabolic pathways, lifespan extension, cell cycle and growth regulation, and circadian rhythms. Twelve targets were prioritized for further analysis, 10 of which were validated by ChIP-quantitative PCR and quantitative real-time PCR. These 10 genes activated by FOXO are highly up-regulated during diapause and are thus strong candidates for implementation of the diapause syndrome.
authors.affiliation: Department of Biology, Baylor University, Waco, TX 76798; cheolho_sim@baylor.edu denlinger.1@osu.edu.
authors.forename: Cheolho
authors.initials: C
authors.lastname: Sim
authors.affiliation: Department of Biology, Baylor University, Waco, TX 76798;
authors.forename: David S
authors.initials: DS
authors.lastname: Kang
authors.affiliation: Department of Biology, Baylor University, Waco, TX 76798;
authors.forename: Sungshil
authors.initials: S
authors.lastname: Kim
authors.affiliation: Departments of Entomology and Evolution, Ecology, and Organismal Biology, Ohio State University, Columbus, OH 43210; and Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Bai
authors.affiliation: Departments of Entomology and Evolution, Ecology, and Organismal Biology, Ohio State University, Columbus, OH 43210; and cheolho_sim@baylor.edu denlinger.1@osu.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Denlinger
mesh_terms: D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle; D047369:Chromatin Immunoprecipitation; D002940:Circadian Rhythm; D003465:Culex / Q000235:genetics* / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016678:Genome; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007605:Juvenile Hormones / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D012621:Seasons; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D051858:Forkhead Transcription Factors; D019476:Insect Proteins; D007328:Insulin; D007605:Juvenile Hormones
keywords: Culex pipiens; diapause; forkhead transcription factor; insulin