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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

1
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
2
Lewis-Sigler Institute for Integrative Genomics and Dept. of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
3
Center for Computational Biology and Bioinformatics, Columbia University Medical Center, New York, NY 10027, USA.
#
Contributed equally

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.

PMID:
23911329
PMCID:
PMC3763726
DOI:
10.1016/j.cell.2013.07.006
[Indexed for MEDLINE]
Free PMC Article

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