Program of the 2001 International Worm Meeting - Sternberg Lab ...

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Thus, while daf-12 plays an important role in
hermaphrodite ageing (as shown by mutant
interactions with daf-2 and its requirement for
lifespan extension resulting from germline
ablation (4)), it appears to play no role in male
ageing. daf-12 encodes a nuclear hormone
receptor (5), which is a candidate gene for the
ultimate receipt and transduction of cell
subset-specific signals from the insulin-like
signalling pathway to control dauer formation
and ageing (5). Our findings reveal sex-specific
differences in genetic pathways regulating
lifespan, and suggest the possibility that daf-12
may not be expressed in adult males.
(1) Gems, D. & Riddle, D.L. (2000) Genetics
154: 1597-1610. (2) Larsen, P.L. et al. (1995)
Genetics 139: 1567-1583. (3) Gems, D. et al.
(1998) Genetics 150: 129-155. (4) Hsin, H. &
Kenyon, C. (1999) Nature 399: 362-366. (5)
Antebi, A. et al. (2000) Genes & Dev 14:
1512-1527.
616. Molecular Identification of
Transcriptional Targets of the
DAF-16 Winged Helix Transcription
Factor
Joshua J. McElwee, James H.
Thomas
University of Washington, Department of
Genetics, J205 Health Sciences Building, Box
357360, Seattle, Washington, 98195-7360
616
Dauer arrest and longevity in C. elegans are
controlled by an insulin-like signaling pathway
transduced by the winged helix transcription
factor DAF-16. Mutations in several genes
within this pathway (daf-2, age-1, and pdk-1)
result in constitutive dauer formation (Daf-c)
and increased lifespan (Age) phenotypes. Both
the Daf-c and Age phenotypes of these mutants
are suppressed by loss of function mutations in
daf-16. This suggests DAF-16 acts as the
principal transcriptional output controlling both
diapause and lifespan governed by this pathway.
We are attempting to identify both direct and
indirect transcriptional targets of DAF-16
utilizing two complementary molecular
approaches. Recently, the DAF-16 consensus
binding element (DBE) was identified by
Furuyama et al (2000). Using the DBE
sequence, we have searched the C. elegans
genomic sequence and identified many genes
that contain the DBE within putative regulatory
regions. To refine this list of possible DAF-16
target genes, we have collaborated with the Kim
lab at Stanford to examine in vivo differences in
gene expression between daf-2 and daf-2;
daf-16 strains using cDNA microarrays. These
two approaches have yielded a small subset of
genes that contain at least one DBE and show a
reproducible expression difference. We are
currently examining the role of these genes in
dauer formation and lifespan determination
using RNAi and transgenic overexpression.