REGULATION OF LIFESPAN BY THE MES-2/3/6 COMPLEX AND H3K27ME3 DEPLETION DURING AGING IN C. ELEGANS
Physical and Biological Sciences
MCD Biology
Aging is a process common to all living organisms and is associated with cellular deterioration and increased risk to disease. Regulation of aging at the molecular level is complex and involves the coordinated interaction of many genes and their protein products. Recently, classes of proteins responsible for regulating the accessibility of DNA and the local environment on genes have been implicated in aging regulation. Inducing an open state of DNA allows for genes to be accessed by transcription machinery, while a closed state discourages access and limits production of gene products. This thesis focuses on the regulation of aging by members of the MES-2/3/6 complex, a protein complex responsible for establishing a compact chromatin state within cells. Here, we show that in Caenorhabditis elegans, a species of nematode worm, the MES-2/3/6 complex regulates lifespan to a moderate degree. This complex induces chromatin compaction by catalyzing the attachment of three methyl groups to the histone proteins that DNA is wrapped around. To determine if levels of these methyl marks change as a worm ages, we tracked the presence of this mark within somatic cells, specifically intestine, over the lifespan of worms and found that qualitatively, H3K27me3 levels decrease over time. This work contributes to our understanding of the regulation of aging in higher order organisms as well as how changes in accessibility to DNA over time might influence aging.
