The structure of chromatin changes dynamically during development and reproduction. Remodeling of chromatin involves highly specialized enzymes. One of them is the evolutionarily conserved chromatin remodeling factor Mi-2, the core subunit of the human NuRD (Nucleosome Remodeling and histone Deacetylase) complex. The gene
let-418 encodes one of the two C. elegans Mi-2 orthologues. Strong loss-of-function alleles of
let-418 show a highly pleiotropic phenotype that includes sterility, vulva defects and a L1 larval arrest associated with ectopic expression of germline specific genes (von Zelewsky et al., 2000; Unhavaithaya et al., 2002). Altogether, these phenotypes suggest an important developmental role of
let-418. Here we report on an additional aspect of the
let-418 phenotype. We observed that loss of
let-418 induces a significant lifespan extension, increases dauer formation and strongly enhances resistance to oxidative and heat stress. Thus, LET-418 may be part of a mechanism that is required to maintain a chromatin state allowing normal growth and reproduction. Reduction or depletion of
let-418 activity results in a shift towards somatic endurance, longevity and sterility. For extension of lifespan and stress resistance
let-418 acts synthetically with
daf-2, suggesting that
let-418 functions in parallel of the insulin pathway. Moreover,
let-418 partly requires the activity of
daf-16. To see, whether
let-418 acts through
daf-16, we tested if depletion of
let-418 influences the localization and/or the expression level of
daf-16 and found that neither of them was changed. To test whether LET-418 may affect the transcriptional activity of DAF-16, we analyzed the expression patterns of the heat shock protein gene
hsp-16.2 and the superoxide dismutase gene
sod-3, which are targets of
daf-16. We found that both genes show elevated mRNA levels in a
let-418 mutant background. The over-expression of
sod-3 mRNA was dependent on DAF-16, whereas that of
hsp-16.2 was totally independent. Currently, we are further investigating the molecular mode of action of LET-418 on the expression of
sod-3 and
hsp-16.2.