Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans

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dc.contributor.authorKumar, N.
dc.contributor.authorJain, V.
dc.contributor.authorSingh, A.
dc.contributor.authorJagtap, U.
dc.contributor.authorVerma, S.
dc.contributor.authorMukhopadhyay, A.
dc.date.accessioned2018-07-14T01:18:48Z
dc.date.accessioned2024-08-14T07:41:15Z
dc.date.available2018-07-14T01:18:48Z
dc.date.available2024-08-14T07:41:15Z
dc.date.issued2015
dc.description.abstractLowering insulin-IGF-1-like signalling (IIS) activates FOXO transcription factors (TF) to extend life span across species. To study the dynamics of FOXO chromatin occupancy under this condition in C. elegans, we report the first recruitment profile of endogenous DAF-16 and show that the response is conserved. DAF-16 predominantly acts as a transcriptional activator and binding within the 0.5 kb promoter-proximal region results in maximum induction of downstream targets that code for proteins involved in detoxification and longevity. Interestingly, genes that are activated under low IIS already have higher DAF-16 recruited to their promoters in WT. DAF- 16 binds to variants of the FOXO consensus sequence in the promoter proximal regions of genes that are exclusively targeted during low IIS. We also define a set of 'core' direct targets, after comparing multiple studies, which tend to co-express and contribute robustly towards IIS-associated phenotypes. Additionally, we show that nuclear hormone receptor DAF-12 as well as zinc-finger TF EOR-1 may bind DNA in close proximity to DAF-16 and distinct TF classes that are direct targets of DAF-16 may be instrumental in regulating its indirect targets. Together, our study provides fundamental insights into the transcriptional biology of FOXO/DAF-16 and gene regulation downstream of the IIS pathway.en_US
dc.identifier.citationKumar, N., Jain, V., Singh, A., Jagtap, U., Verma, S., & Mukhopadhyay, A. (2015). Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans. Oncotarget, 6(39), 41418-41433. doi: 10.18632/oncotarget.6282en_US
dc.identifier.doi10.18632/oncotarget.6282
dc.identifier.issn19492553
dc.identifier.urihttp://10.2.3.109/handle/32116/1343
dc.identifier.urlhttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=6282&path[]=16324
dc.language.isoen_USen_US
dc.publisherImpact Journals LLCen_US
dc.subjectInsulinen_US
dc.subjectProtein Eor 1en_US
dc.subjectTranscription Factoren_US
dc.subjectTranscription Factor Daf 16en_US
dc.subjectTranscription Factor Foxoen_US
dc.subjectUnclassified Drugen_US
dc.subjectCaenorhabditis Elegans Proteinen_US
dc.subjectCell Receptoren_US
dc.subjectDaf-12 Protein, C Elegansen_US
dc.subjectDaf-16 Protein, C Elegansen_US
dc.subjectDaf-2 Protein, C Elegansen_US
dc.subjectDrosophila Proteinen_US
dc.subjectEor-1 Protein, C Elegansen_US
dc.subjectForkhead Transcription Factoren_US
dc.subjectFoxo Protein, Drosophilaen_US
dc.subjectFoxo3 Protein, Humanen_US
dc.subjectInsulinen_US
dc.subjectInsulin Receptoren_US
dc.subjectNuclear Proteinen_US
dc.subjectTranscription Factor Fkhrl1 Caenorhabditis Elegansen_US
dc.subjectChromatinen_US
dc.subjectChromatinen_US
dc.titleGenome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegansen_US
dc.title.journalOncotarget
dc.typeArticleen_US

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