Age-Dependent Changes in Transcription Factor FOXO Targeting in Female Drosophila

dc.contributor.author Birnbaum, Allison
dc.contributor.author Wu, Xiaofen
dc.contributor.author Bai, Hua
dc.contributor.author Tatar, Marc
dc.contributor.author Liu, Nan
dc.contributor.author Bai, Hua
dc.contributor.department Genetics, Development and Cell Biology
dc.date 2020-06-12T15:27:38.000
dc.date.accessioned 2020-06-30T04:02:20Z
dc.date.available 2020-06-30T04:02:20Z
dc.date.copyright Tue Jan 01 00:00:00 UTC 2019
dc.date.issued 2019-05-01
dc.description.abstract <p>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 (2-week-old) and aged (5-week-old) wild-type female 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 (FOXOrepressing genes) or down-regulated (FOXO-activating genes) in adult head tissue. 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 female flies. FOXO targeting on these pathways decreases with age. Interestingly, FOXO targets in aged 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.</p>
dc.description.comments <p>This article is published as Birnbaum, Allison, Xiaofen Wu, Marc Tatar, Nan Liu, and Hua Bai. "Age-dependent changes in transcription factor FOXO targeting in female Drosophila." <em>Frontiers in genetics</em> 10 (2019): 312. doi: <a href="https://doi.org/10.3389/fgene.2019.00312">10.3389/fgene.2019.00312</a>.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/gdcb_las_pubs/254/
dc.identifier.articleid 1257
dc.identifier.contextkey 18077397
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath gdcb_las_pubs/254
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/37932
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/gdcb_las_pubs/254/2019_Bai_AgeDependent.pdf|||Fri Jan 14 22:58:28 UTC 2022
dc.source.uri 10.3389/fgene.2019.00312
dc.subject.disciplines Cell Biology
dc.subject.disciplines Developmental Biology
dc.subject.disciplines Genetics
dc.subject.keywords forkhead transcription factor FOXO
dc.subject.keywords ChIP-Seq
dc.subject.keywords transcriptional regulation
dc.subject.keywords longevity control
dc.subject.keywords insulin
dc.subject.keywords hippo
dc.subject.keywords MAPK
dc.subject.keywords histone
dc.title Age-Dependent Changes in Transcription Factor FOXO Targeting in Female Drosophila
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication ae16dcee-afdf-4805-9590-eb7a0bb1d0f1
relation.isOrgUnitOfPublication 9e603b30-6443-4b8e-aff5-57de4a7e4cb2
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