Transcriptional profile of C. elegans fed E. coli (OP50) and B. subtilis (PY79)

We used RNA-seq to assay gene expression changes over time in response to OP50 and PY79 To understand the molecular processes underlying aging, we screened modENCODE ChIP-seq data to identify transcription factors that bind to age-regulated genes in C. elegans. The most significant hit was the GATA transcription factor encoded by elt-2, which is responsible for inducing expression of intestinal genes during embryogenesis. Expression of ELT-2 decreases during aging, beginning in middle age. We identified genes regulated by ELT-2 in the intestine during embryogenesis, and then showed that these developmental genes markedly decrease in expression as worms grow old. Overexpression of elt-2 extends lifespan and slows the rate of gene expression changes that occur during normal aging. Thus, our results identify the developmental regulator ELT-2 as a major driver of normal aging in C. elegans. Overall design: Whole-worm mRNA was sequenced from E. coli- and B.subtilis-fed worms. For each condidtion, one replicate was sequenced at Day 4 and Day 13

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Mann FG, Van Nostrand EL, Friedland AE, Liu X, Kim SK