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Age-dependent changes in transcription factor FOXO targeting in Drosophila melanogaster

Allison Birnbaum,Xiaofeng Wu,M. Tatar,Nan Liu,Hua Bai

Published 2018 in bioRxiv

ABSTRACT

FOXO transcription factors have long been associated with longevity and tissue homeostasis. Although direct targets of FOXO have been reported in various long-lived mutants or stress conditions (nutrient deprivation), no studies have investigated how normal aging impacts the transcriptional activity of FOXO. Here, we conducted chromatin immunoprecipitation sequencing in both young and old wild-type fruit flies, Drosophila melanogaster, to evaluate the dynamics of FOXO gene targeting during aging. Drosophila FOXO binds to 2617 genes at young ages, whereas the number of FOXO-bound genes dramatically decreases to 224 at old ages. Consistently, many genes bound by FOXO in young flies are transcriptionally altered with age, including genes in Hippo and MAPK signaling pathways. Interestingly, we also find that many FOXO-bound genes in wild-type flies are unique from those in insulin mutants, suggesting FOXO is regulated by multiple upstream inputs. Together, these results provide new insights into dynamic FOXO targeting under normal aging and highlight the diverse regulatory mechanisms for FOXO transcriptional activity that are currently less understood.

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