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Cell. 2013 Aug 1;154(3):676-690. doi: 10.1016/j.cell.2013.07.006.

PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.

Author information

Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Lewis-Sigler Institute for Integrative Genomics and Dept. of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, NY 10027, USA.
Contributed equally


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.

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