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

TitlePQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.
Publication TypeJournal Article
Year of Publication2013
AuthorsTepper RG, Ashraf J, Kaletsky R, Kleemann G, Murphy CT, Bussemaker HJ
JournalCell
Volume154
Issue3
Pagination676-690
Date Published2013 Aug 01
ISSN1097-4172
KeywordsAnimals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Forkhead Transcription Factors, Gene Expression Regulation, Developmental, Longevity, Receptor, Insulin, Regulatory Sequences, Nucleic Acid, Trans-Activators, Transcription Factors, Transcriptional Activation
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.

DOI10.1016/j.cell.2013.07.006
Alternate JournalCell
PubMed ID23911329
PubMed Central IDPMC3763726
Grant ListR01 HG003008 / HG / NHGRI NIH HHS / United States
R01AG034446 / AG / NIA NIH HHS / United States
P50GM071508 / GM / NIGMS NIH HHS / United States
U54CA121852 / CA / NCI NIH HHS / United States
DP2 OD004402 / OD / NIH HHS / United States
R01 AG034446 / AG / NIA NIH HHS / United States
DP2OD004402 / OD / NIH HHS / United States
R01HG003008 / HG / NHGRI NIH HHS / United States
P50 GM071508 / GM / NIGMS NIH HHS / United States
U54 CA121852 / CA / NCI NIH HHS / United States