Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans
Loading...
Files
Date
2015
Journal Title
Journal ISSN
Volume Title
Publisher
Impact Journals LLC
Abstract
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.
Description
Keywords
Insulin, Protein Eor 1, Transcription Factor, Transcription Factor Daf 16, Transcription Factor Foxo, Unclassified Drug, Caenorhabditis Elegans Protein, Cell Receptor, Daf-12 Protein, C Elegans, Daf-16 Protein, C Elegans, Daf-2 Protein, C Elegans, Drosophila Protein, Eor-1 Protein, C Elegans, Forkhead Transcription Factor, Foxo Protein, Drosophila, Foxo3 Protein, Human, Insulin, Insulin Receptor, Nuclear Protein, Transcription Factor Fkhrl1 Caenorhabditis Elegans, Chromatin, Chromatin
Citation
Kumar, 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.6282