547C Poster - 07. Chromatin, epigenetics and genomics
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Clara Guida; Georg Vogler; Peter Adams; Rolf Bodmer

Affiliation: Sanford Burnham Prebys Medical Discovery Institute

Keywords:
g. Polycomb/trithorax complexes; j. cardiovascular disease

The incidence of heart failure approximately doubles through each decade of life. The detrimental effects of age on heart function are likely due in part to epigenetic dysregulation and associated gene program changes. Indeed, evidence already suggests that the maintenance of the epigenome becomes more error-prone with age, leading to so-called “epigenetic drift”, or accumulation of epigenetic alterations. Interestingly, manipulation of certain epigenetic modifiers was found to expand lifespan in different animal models. However, little is known about the epigenetic mechanism underlying cardiac aging. The challenge of studying cardiac aging relies in part on the low abundance of human samples and long and expensive experimental times for mammalian animal models. Here we used the Drosophila heart model, which has several advantages including short lifespan, less genetic redundancy, conserved biological pathways, and in vivo heart analysis protocols, to identify epigenetic mechanisms involved in cardiac aging. In a targeted genetic screen, we found that partial depletion of components of the Polycomb Repressive Complex 2 (PRC2) prevented cardiac aging. This is in line with previous findings reporting increased lifespan in PRC2^+/- flies. Indeed, we found that H3K27me3 content is increased in cardiomyocytes with age in control flies. Moreover, age-related cardioprotection was also achieved when we treated flies with an inhibitor of the H3K27me3 methyltransferase, EZH2. These findings suggest that H3K27me3 marks can mediate age-related heart function deterioration and establish the Drosophila model as a useful tool to investigate the basic biology of age-related cardiac epigenetic drift.