Source:http://linkedlifedata.com/resource/pubmed/id/20706209
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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
2010-8-13
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pubmed:abstractText |
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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caenorhabditis elegans Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Site-Specific...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/daf-16 protein, C elegans
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1744-4292
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pubmed:author |
pubmed-author:DoonanRyanR,
pubmed-author:GemsDavidD,
pubmed-author:HopeIan AIA,
pubmed-author:MatthijssensFilipF,
pubmed-author:McElweeJoshua JJJ,
pubmed-author:Reece-HoyesJohn SJS,
pubmed-author:SchusterEugeneE,
pubmed-author:ThorntonJanet MJM,
pubmed-author:TulletJennifer M AJM,
pubmed-author:VanfleterenJacques RJR
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
399
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pubmed:meshHeading |
pubmed-meshheading:20706209-Animals,
pubmed-meshheading:20706209-Binding Sites,
pubmed-meshheading:20706209-Caenorhabditis elegans,
pubmed-meshheading:20706209-Caenorhabditis elegans Proteins,
pubmed-meshheading:20706209-Chromatin,
pubmed-meshheading:20706209-DNA Methylation,
pubmed-meshheading:20706209-Forkhead Transcription Factors,
pubmed-meshheading:20706209-Gene Expression Profiling,
pubmed-meshheading:20706209-Gene Expression Regulation, Developmental,
pubmed-meshheading:20706209-Longevity,
pubmed-meshheading:20706209-RNA, Messenger,
pubmed-meshheading:20706209-Site-Specific DNA-Methyltransferase (Adenine-Specific),
pubmed-meshheading:20706209-Transcription Factors
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pubmed:year |
2010
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pubmed:articleTitle |
DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO.
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pubmed:affiliation |
Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, London, UK. e.schuster@ucl.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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