To unveil the mechanisms underlying aging in C. elegans, we have carried out microarray analysis to profile changes in gene expression between young and old worms. Bioinformatics analysis revealed that the promoters of the 1254 age-regulated genes are highly enriched for the GATA binding motif. We previously found that age-related changes in expression of many of these genes are caused by three GATA transcription factors (
elt-3,
elt-5 and
elt-6)(Budovskaya et al., Cell 2008). Here, we identify an additional GATA transcription factor,
egl-27, that plays an important role during the aging process. We found that loss-of-function and gain-of-function alleles of
egl-27 have opposite effects on lifespan; specifically, overexpression of
egl-27 extends lifespan and knockdown of
egl-27 decreases
daf-2 lifespan without affecting wild-type lifespan. These results indicate that levels of
egl-27(+) play a critical role in promoting longevity. To determine how
egl-27 promotes longevity, we performed ChIP-seq analysis to find EGL-27 targets. We found that EGL-27 targets are highly enriched for genes whose expressions decrease with age, suggesting that EGL-27 plays a direct role in regulating the aging process. Further, we found that slow aging
daf-2 mutants exhibit increased
egl-27 expression while fast aging
elt-3 mutants display decreased
egl-27 expression, suggesting that
egl-27 acts downstream of insulin signaling and GATA transcriptional networks. In addition to the GATA DNA binding domain, EGL-27 is homologous to mammalian metastasis tumor antigen 1 (MTA1) family, which functions as part of the nucleosome remodeling and decacetylase (NuRD) complex. This raises the possibility that changes in EGL-27 in old worms affect not only the GATA transcriptional network but also chromatin structure in general.