Nature Genetics 38, 251 - 257 (2005)
Published online: 25 December 2005; | doi:10.1038/ng1723
Identification of direct DAF-16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitationSeung Wook Oh1, 3, Arnab Mukhopadhyay1, 3, Bharat L Dixit1, Tamal Raha1, Michael R Green1, 2
& Heidi A Tissenbaum11
Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. 2
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. 3
These authors contributed equally to this work.
Correspondence should be addressed to Heidi A Tissenbaum heidi.tissenbaum@umassmed.edu 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.
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