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

Eugene Schuster, Joshua J McElwee, Jennifer MA Tullet, Ryan Doonan, Filip Matthijssens UGent, John S Reece-Hoyes, Ian A Hope, Jacques Vanfleteren UGent, Janet M Thornton and David Gems (2010) MOLECULAR SYSTEMS BIOLOGY. 6.
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-functional TF 'parking sites'. This study demonstrates the efficacy of DamID for chromatin profiling in C. elegans.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
C. elegans, aging, DAF-16/FoxO, DamID chromatin profiling, transcriptional networks, CAENORHABDITIS-ELEGANS, LIFE-SPAN, IDENTIFICATION, GENES, LONG, METHYLTRANSFERASE, EXPRESSION, PATTERNS, MUTANTS, SIGNALS
journal title
MOLECULAR SYSTEMS BIOLOGY
Mol. Syst. Biol.
volume
6
article_number
399
pages
6 pages
Web of Science type
Article
Web of Science id
000284527700008
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
9.667 (2010)
JCR rank
19/284 (2010)
JCR quartile
1 (2010)
ISSN
1744-4292
DOI
10.1038/msb.2010.54
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1999125
handle
http://hdl.handle.net/1854/LU-1999125
date created
2012-01-20 16:25:25
date last changed
2012-01-26 15:22:32
@article{1999125,
  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-functional TF 'parking sites'. This study demonstrates the efficacy of DamID for chromatin profiling in C. elegans.},
  articleno    = {399},
  author       = {Schuster, Eugene and McElwee, Joshua J and Tullet, Jennifer MA and Doonan, Ryan and Matthijssens, Filip and Reece-Hoyes, John S and Hope, Ian A and Vanfleteren, Jacques and Thornton, Janet M and Gems, David },
  issn         = {1744-4292},
  journal      = {MOLECULAR SYSTEMS BIOLOGY},
  keyword      = {C. elegans,aging,DAF-16/FoxO,DamID chromatin profiling,transcriptional networks,CAENORHABDITIS-ELEGANS,LIFE-SPAN,IDENTIFICATION,GENES,LONG,METHYLTRANSFERASE,EXPRESSION,PATTERNS,MUTANTS,SIGNALS},
  language     = {eng},
  pages        = {6},
  title        = {DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO},
  url          = {http://dx.doi.org/10.1038/msb.2010.54},
  volume       = {6},
  year         = {2010},
}

Chicago
Schuster, Eugene, Joshua J McElwee, Jennifer MA Tullet, Ryan Doonan, Filip Matthijssens, John S Reece-Hoyes, Ian A Hope, Jacques Vanfleteren, Janet M Thornton, and David Gems. 2010. “DamID in C. Elegans Reveals Longevity-associated Targets of DAF-16/FoxO.” Molecular Systems Biology 6.
APA
Schuster, E., McElwee, J. J., Tullet, J. M., Doonan, R., Matthijssens, F., Reece-Hoyes, J. S., Hope, I. A., et al. (2010). DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO. MOLECULAR SYSTEMS BIOLOGY, 6.
Vancouver
1.
Schuster E, McElwee JJ, Tullet JM, Doonan R, Matthijssens F, Reece-Hoyes JS, et al. DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO. MOLECULAR SYSTEMS BIOLOGY. 2010;6.
MLA
Schuster, Eugene, Joshua J McElwee, Jennifer MA Tullet, et al. “DamID in C. Elegans Reveals Longevity-associated Targets of DAF-16/FoxO.” MOLECULAR SYSTEMS BIOLOGY 6 (2010): n. pag. Print.