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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Developmental*
  • Longevity*
  • Receptor, Insulin / metabolism
  • Regulatory Sequences, Nucleic Acid
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • Transcriptional Activation


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • PQM-1 protein, C elegans
  • Trans-Activators
  • Transcription Factors
  • daf-16 protein, C elegans
  • DAF-2 protein, C elegans
  • Receptor, Insulin