DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO

Molecular Systems Biology
Eugene F SchusterDavid Gems

Abstract

Insulin/IGF-1 signaling controls metabolism, stress resistance and aging in Caenorhabditis elegans by regulating the activity of the DAF-16/FoxO transcription factor (TF). However, the function of DAF-16 and the topology of the transcriptional network that it crowns remain unclear. Using chromatin profiling by DNA adenine methyltransferase identification (DamID), we identified 907 genes that are bound by DAF-16. These were enriched for genes showing DAF-16-dependent upregulation in long-lived daf-2 insulin/IGF-1 receptor mutants (P=1.4e(-11)). Cross-referencing DAF-16 targets with these upregulated genes (daf-2 versus daf-16; daf-2) identified 65 genes that were DAF-16 regulatory targets. These 65 were enriched for signaling genes, including known determinants of longevity, but not for genes specifying somatic maintenance functions (e.g. detoxification, repair). This suggests that DAF-16 acts within a relatively small transcriptional subnetwork activating (but not suppressing) other regulators of stress resistance and aging, rather than directly regulating terminal effectors of longevity. For most genes bound by DAF-16::DAM, transcriptional regulation by DAF-16 was not detected, perhaps reflecting transcriptionally non-function...Continue Reading

Associated Datasets

References

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Citations

May 28, 2013·BMC Systems Biology·Graham R Smith, Daryl P Shanley
Sep 27, 2013·PLoS Genetics·Meredith E JudyAimee W Kao
Nov 30, 2012·Annual Review of Physiology·David Gems, Linda Partridge
Sep 19, 2015·Wiley Interdisciplinary Reviews. Developmental Biology·Gabriel N Aughey, Tony D Southall
Jul 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Mihwa SeoSeung-Jae V Lee
Jun 29, 2011·Free Radical Biology & Medicine·Piotr Zimniak
Jan 24, 2013·Molecular Systems Biology·Astrid EijkelenboomBoudewijn M T Burgering
Mar 30, 2011·Aging Cell·Cathy SlackLinda Partridge
Mar 24, 2016·Nucleic Acids Research·Alexey V PindyurinBas van Steensel
Oct 4, 2011·Current Opinion in Genetics & Development·Eric L Van Nostrand, Stuart K Kim
Dec 24, 2013·Cell Reports·Astrid EijkelenboomBoudewijn M T Burgering
Apr 15, 2014·Cell Metabolism·Kristopher BurkewitzWilliam B Mair
Jan 21, 2014·Neuron·Alexandra B ByrneMarc Hammarlund
May 3, 2013·Nature Cell Biology·Ashley E Webb, Anne Brunet
Nov 2, 2016·Development·Jose Arturo Gutierrez-TrianaJoachim Wittbrodt
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Jun 30, 2018·Molecular Biology and Evolution·Laura M JonesPeter E Urwin
Oct 23, 2015·Nature Communications·Gabriel E ZentnerSteven Henikoff
Dec 17, 2015·The Journal of Biological Chemistry·Qing ChenMorris J Birnbaum

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Datasets Mentioned

BETA
E-MEXP-2414

Methods Mentioned

BETA
immunoprecipitation
DamID
ChIP-PCR
PCR
ChIP
ChIP-Seq

Software Mentioned

expression analysis systematic explorer ( EASE )
Ringo package
Excel
R
EASE
DamID
Bioconductor

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