Role of DVE-1 and higher chromatin organization in ageing of Caenorhabditis elegans

Abstract

The competency of an organism to sense the stressful conditions and appropriately respond to them determines its survivability. Insulin/IGF-1 signaling is one of the most studied pathways that sense different stress conditions and its downstream effector, DAF-16/FOXO modulates the expression level of various stress-responsive and pro-longevity genes. However, the ability of this pathway to suffice for the necessary transcriptional changes in diverse stress conditions remains elusive. In the first study, using C. elegans as the model system we for the first time show that DAF-16 forms complex with a homeobox transcription factor, DVE-1 and binds to the promoters of a large number of longevity genes. This complex formation may have a combinatorial effect in setting different transcriptional paradigms appropriate for the survival of organisms in different stress conditions. In a separate study, we investigated a mutation in dve-1 gene that conferred longevity and exceptional stress-responsive capabilities to the worms. Using high-throughput experiments and additional biochemical techniques, we dissected out the mechanisms that led to these observed phenotypes in the mutant worms. These findings strengthen our understanding of how various transcription factors act as a part of a transcription module that senses the stressful conditions and establishes global gene expression patterns to mitigate stress and promote longevity.