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Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans
Lowering 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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747164/ https://www.ncbi.nlm.nih.gov/pubmed/26539642 |
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author | Kumar, Neeraj Jain, Vaibhav Singh, Anupama Jagtap, Urmila Verma, Sonia Mukhopadhyay, Arnab |
author_facet | Kumar, Neeraj Jain, Vaibhav Singh, Anupama Jagtap, Urmila Verma, Sonia Mukhopadhyay, Arnab |
author_sort | Kumar, Neeraj |
collection | PubMed |
description | Lowering 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. |
format | Online Article Text |
id | pubmed-4747164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47471642016-03-25 Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans Kumar, Neeraj Jain, Vaibhav Singh, Anupama Jagtap, Urmila Verma, Sonia Mukhopadhyay, Arnab Oncotarget Research Paper: Gerotarget (Focus on Aging) Lowering 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. Impact Journals LLC 2015-11-02 /pmc/articles/PMC4747164/ /pubmed/26539642 Text en Copyright: © 2015 Kumar et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper: Gerotarget (Focus on Aging) Kumar, Neeraj Jain, Vaibhav Singh, Anupama Jagtap, Urmila Verma, Sonia Mukhopadhyay, Arnab Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans |
title | Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans |
title_full | Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans |
title_fullStr | Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans |
title_full_unstemmed | Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans |
title_short | Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans |
title_sort | genome-wide endogenous daf-16/foxo recruitment dynamics during lowered insulin signalling in c. elegans |
topic | Research Paper: Gerotarget (Focus on Aging) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747164/ https://www.ncbi.nlm.nih.gov/pubmed/26539642 |
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