title: Identification of direct DAF-16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitation.
abstract: DAF-16, a forkhead transcription factor, is a key regulator of longevity, metabolism and dauer diapause in Caenorhabditis elegans. The precise mechanism by which DAF-16 regulates multiple functions, however, is poorly understood. Here, we used chromatin immunoprecipitation (ChIP) to identify direct targets of DAF-16. We cloned 103 target sequences containing consensus DAF-16 binding sites and selected 33 targets for further analysis. Expression of most of these genes is regulated in a DAF-16-dependent manner, and inactivation of more than half of these genes significantly altered DAF-16-dependent functions, including life span, fat storage and dauer formation. Our results show that the ChIP-based cloning strategy leads to greater enrichment for DAF-16 target genes than previous screening strategies. We also demonstrate that DAF-16 is recruited to multiple promoters to coordinate regulation of its downstream targets. The large number of target genes discovered provides insight into how DAF-16 controls diverse biological functions.
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Seung Wook
authors.initials: SW
authors.lastname: Oh
authors.forename: Arnab
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Bharat L
authors.initials: BL
authors.lastname: Dixit
authors.forename: Tamal
authors.initials: T
authors.lastname: Raha
authors.forename: Michael R
authors.initials: MR
authors.lastname: Green
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Tissenbaum
mesh_terms: D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D008136:Longevity / Q000502:physiology*; D010641:Phenotype; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans