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

Allison Birnbaum, Xiaofen Wu, Marc Tatar, Nan Liu, Hua Bai
doi: https://doi.org/10.1101/456426
Allison Birnbaum
1Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA
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Xiaofen Wu
2Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, 201210, China
3University of Chinese Academy of Sciences, Beijing, 100049, China
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Marc Tatar
4Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, 02912, USA
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Nan Liu
2Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, Shanghai, 201210, China
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Hua Bai
1Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA
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Summary

FOXO transcription factors have long been associated with longevity control and tissue homeostasis. Although the transcriptional regulation of FOXO have been previously characterized (especially in long-lived insulin mutants and under stress conditions), how normal aging impacts the transcriptional activity of FOXO is poorly understood. Here, we conducted a chromatin immunoprecipitation sequencing (ChIP-Seq) analysis in both young and old wild-type fruit flies, Drosophila melanogaster, to evaluate the dynamics of FOXO gene targeting during aging. Intriguingly, the number of FOXO-bound genes dramatically decreases with age (from 2617 to 224). Consistent to the reduction of FOXO binding activity, many genes targeted by FOXO in young flies are transcriptionally altered with age, either up-regulated (FOXO-repressing genes) or down-regulated (FOXO-activating genes). In addition, we show that many FOXO-bound genes in wild-type flies are unique from those in insulin receptor substrate chico mutants. Distinct from chico mutants, FOXO targets specific cellular processes (e.g., actin cytoskeleton) and signaling pathways (e.g., Hippo, MAPK) in young wild-type flies. FOXO targeting on these pathways decreases with age. Interestingly, FOXO targets in old flies are enriched in cellular processes like chromatin organization and nucleosome assembly. Furthermore, FOXO binding to core histone genes is well maintained at aged flies. Together, our findings provide new insights into dynamic FOXO targeting under normal aging and highlight the diverse and understudied regulatory mechanisms for FOXO transcriptional activity.

Footnotes

  • Email: Allison Birnbaum: abirnba1{at}iastate.edu, Xiaofen Wu: xiaofenwu{at}sioc.ac.cn, Marc Tatar: Marc_Tatar{at}brown.edu, Nan Liu: liunan{at}sioc.ac.cn, Hua Bai: hbai{at}iastate.edu

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 13, 2018.
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Age-dependent changes in transcription factor FOXO targeting in Drosophila melanogaster
Allison Birnbaum, Xiaofen Wu, Marc Tatar, Nan Liu, Hua Bai
bioRxiv 456426; doi: https://doi.org/10.1101/456426
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Age-dependent changes in transcription factor FOXO targeting in Drosophila melanogaster
Allison Birnbaum, Xiaofen Wu, Marc Tatar, Nan Liu, Hua Bai
bioRxiv 456426; doi: https://doi.org/10.1101/456426

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