Genome-Wide DNA Methylation And Transcription Factor Fkh Regulatory Mechanism In Dietary Restriction Mediated Drosophila Lifespan Extension

Dietary restriction has been considered as one of the important dietary intervention to extend organism’s lifespan.Aging and epigenetics orcircadian rhythms are always interwined.In the present study,wecharacterized the unique methylome of adult Drosophila melanogaster using highly advanced whole-genome bisulfite sequencing in dietary restricted and fully fed flies.On the other hand,we also used the 24 hours time-course microarray to identify transcripts that oscillate in wildtype（Canton-S）andmutant flies(Timeless⁰¹)on ad libitum and dietary restriction diets.The main results are as follows:（1）The Drosophila melanogaster methylomes have a mosaic pattern under both conditions.The CG,CHG and CHH sites coexist in the genome and more than half of the methylated cytosine sites are located in CHH site;there does indeed exists the cytosine methylation in adult fruit flies,but the methylation level is very low;there is no significantly difference between ad libitum（0.29%）and dietary restricted（0.27%）flies,which suggests the involvement of other epigenetic modifications rather than the direct role of DNA methylation in anti-aging effects of dietary restriction.（2）Based on the time-course microarray analysis,we found that dietary restriction enhanced core clock gene amplitude.Gene-ontology analysis of the dietary restriction circadian transcriptome indicated a significant enrichment on genes for epithelial and digestive track development,peaking at the beginning of the inactive/night phase.Among them,the circadian transcription factor Fkh is responsible for the core clock gene amplitude,intestinal epithelial integrity and the intestinal circadian rhythm,and thus inducing the lifespan effects through the upstream TOR pathway and the downstream JAK/STAT pathway.But it needs to be explored further in the protein level between Fkh and the core clock genes or clock controlled genes.