title: PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.
abstract: Reduced insulin/IGF-1-like signaling (IIS) extends C. elegans lifespan by upregulating stress response (class I) and downregulating other (class II) genes through a mechanism that depends on the conserved transcription factor DAF-16/FOXO. By integrating genome-wide mRNA expression responsiveness to DAF-16 with genome-wide in vivo binding data for a compendium of transcription factors, we discovered that PQM-1 is the elusive transcriptional activator that directly controls development (class II) genes by binding to the DAF-16-associated element (DAE). DAF-16 directly regulates class I genes only, through the DAF-16-binding element (DBE). Loss of PQM-1 suppresses daf-2 longevity and further slows development. Surprisingly, the nuclear localization of PQM-1 and DAF-16 is controlled by IIS in opposite ways and was also found to be mutually antagonistic. We observe progressive loss of nuclear PQM-1 with age, explaining declining expression of PQM-1 targets. Together, our data suggest an elegant mechanism for balancing stress response and development.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tepper
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics and Dept. of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Ashraf
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics and Dept. of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kaletsky
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics and Dept. of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kleemann
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics and Dept. of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Coleen T
authors.initials: CT
authors.lastname: Murphy
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.|Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, NY 10027, USA.
authors.forename: Harmen J
authors.initials: HJ
authors.lastname: Bussemaker
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D008136:Longevity; D011972:Receptor, Insulin / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C583955:PQM-1 protein, C elegans; D015534:Trans-Activators; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin
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