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Endogenous DAF-16 genome-wide recruitment under low Insulin signaling condition in Caenorhabditis elegans

ABSTRACT: In order to understand the complexity of gene regulation downstream of IIS, we used anti-DAF-16 antibody, we report the first genome-wide ChIP-sequencing study of endogenous DAF-16 recruitment in daf-2(e1370). We also report the average bin-wise normalized read count of ZFP-1 and DAF-16 on DAF-16 summits ChIP-Seq profile of DAF-16 in mix stage

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: Arnab Mukhopadhyay

PROVIDER: E-GEOD-63865 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Kumar Neeraj N Jain Vaibhav V Singh Anupama A Jagtap Urmila U Verma Sonia S Mukhopadhyay Arnab A

Oncotarget 20151201 39

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 inv ...[more]

PMID: 26539642

Similar Datasets

Endogenous DAF-16 genome-wide recruitment under low Insulin signalling condition in Caenorhabditis elegans

Project description:In order to understand the complexity of gene regulation downstream of IIS, we did RNA-seq in mixed culture in wild-type, daf-2(e1370), daf-16(mgDf50);daf-2(e1370) and daf-2(e1370);daf-12(m20 and correlated it with ChIP-seq data RNA-seq profile of different mutants in mix stage

2016-03-01 | E-GEOD-67975 | biostudies-arrayexpress

Transcription profiling of long-lived C.elegans daf-2 pathway mutants with wild type/short-lived mutants

Project description:Comparison of long-lived daf-2 pathway mutants with wild type/short-lived mutants. A: age-1 fer-15; fem-1 vs. fer-15; fem-1. B: age-1 fer-15; fem-1 vs. fer-15; fem-1. C: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. D: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. E: daf-16::gfp in daf-16(mu86);daf-2(e1370) vs. daf-16(mu86);daf-2(e1370). F: daf-2(e1368); fer-15; fem-1 vs. fer-15; fem-1. G: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. H: age-1 fer-15; fem-1 vs. fer-15; fem-1. I: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. J: daf-16::gfp in daf-2(e1370); daf-16(mu86) vs. daf-2(e1370); daf-16(mu86). K: daf-2(mu150) vs. wild type. L: daf-2(e1370) vs. daf-2(e1370); daf-16(mu86). M: daf-2(e1370) vs. daf-2(e1370); daf-16(mu86). N: daf-2(e1370) vs. daf-2(e1370); daf-16(mu86).

2003-07-17 | E-MEXP-7 | biostudies-arrayexpress

wt vs daf-2 C. elegans protein turnover

Project description:Most aging hypotheses revolve around the accumulation of some sort of damage resulting in gradual physiological decline and ultimately death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend lifespan. However, lowering translational efficiency extends rather than shortens lifespan in C. elegans. We studied turnover of individual proteins in the conserved Insulin/Insulin-like Growth Factor (IGF-1) receptor mutant daf-2 by combining Stable Isotope Labeling by Nitrogen-15 in Caenorhabditis elegans and LC-MS/MS. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, while others remained unchanged, signifying that longevity is not supported by high protein turnover. This slow-down of protein turnover was most prominent for components of the translation machinery and mitochondria. In contrast, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged in daf-2. The slow-down of protein dynamics and decreased abundance of the translational machinery may point at the importance of anabolic attenuation in lifespan extension as suggested by the hyperfunction theory.

2016-09-27 | PXD002317 | Pride

Reduced insulin/IGF-1 signaling restores the dynamic properties of key stress granule proteins during aging

Project description:Low complexity “prion-like” domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components including stress granule proteins become highly insoluble with age in C. elegans and that reduced insulin/IGF-1 daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress granule-related RBP aggregates are associated with reduced fitness. We show that HSF-1 is a main regulator of stress granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress granule-related RBPs partly by reducing the build-up of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases.

2017-01-16 | PXD003451 | Pride

Deep sequencing of small RNAs from C. elegans during aging

Project description:Aging is under genetic control in C. elegans but the mechanisms of lifespan regulation are not completely known. MicroRNAs (miRNAs) regulate various aspects of development and metabolism and one miRNA has been previously implicated in lifespan. Here we show that multiple miRNAs change expression in C. elegans aging, including novel miRNAs, and that mutations in several of the most up-regulated miRNAs lead to lifespan defects. Some act to promote normal lifespan and stress resistance while others inhibit these phenomena. We find that these miRNAs genetically interact with genes in the DNA damage checkpoint response pathway and in the insulin signaling pathway. Our findings reveal that miRNAs both positively and negatively influence lifespan. Since several miRNAs up-regulated during aging regulate genes in conserved pathways of aging and thereby influence lifespan in C. elegans, we propose that miRNAs may play important roles in stress response and aging of more complex organisms. 4 sample examined: Wild-type (N2) and long-lived daf-2(e1379) animals at days 0 and 10 of adulthood

2011-01-01 | E-GEOD-24510 | biostudies-arrayexpress

Adult C. elegans: Control daf-2 mutants treated with daf-16 RNAi vs. daf-2 mutants treated with empty vector RNAi

Project description:Transcriptional profiling of adult C. elegans comparing daf-16(-); daf-2(-) animals with adult daf-2(-) animals. Two-condition experiment, daf-2 mutants treated with daf-16 RNAi vs. daf-2 mutants treated with empty vector RNAi. Biological replicates: 8 daf-2 mutants treated with daf-16 RNAi vs. daf-2 mutants treated with empty vector RNAi, independently grown and harvested. One replicate per array.

2010-05-16 | E-GEOD-18561 | biostudies-arrayexpress

Methylation profiling of C.elegans to identify DAF-16 binding

Project description:Profiling of DAF-16 binding by comparison of DNA methylation of a C. elegans control strain expressing the DNA adenine methyltransferase (DAM) and an experimental strain expressing a DAF-16::DAM. Both strains were fed daf-2 RNAi to identify DAF-16 binding associated with long lived worms.

2010-03-01 | E-MEXP-2414 | biostudies-arrayexpress

RNA sequencing analysis of DAF-16 target gene expression when math-33 function is genetically inactivated

Project description:In this study we have investigated the effect of loss of math-33 activity on DAF-16-mediated target gene regulation in C. elegans under conditions of reduced Insulin/IGF-1 signaling (IIS). Using whole nematode RNA sequencing experiments we found that the daf-2(e1370)-mediated induction and repression of DAF-16 target genes was decreased in daf-2(e1370); math-33(tm3561) mutant animals. Our data suggest that the downregulation of endogenous DAF-16 isoforms in the absence of a functional MATH-33 severely affects the global expression of DAF-16 targets when IIS activity is reduced. Therefore, MATH-33 is essential for DAF-16-mediated target gene activation and repression in the context of IIS. DAF-16 mediated target gene regulation was analyzed in daf-2(e1370) nematodes and compared to daf-2(e1370); math-33(tm3561) mutant animals. daf-16(mu86); daf-2(e1370); N2 (wild type) and math-33(tm3561) single mutant animals were used as controls.

2016-06-22 | E-GEOD-70117 | biostudies-arrayexpress

Defining changes in the total levels of proteins during aging of C. elegans

Project description:We performed label-free proteomics in C. elegans to define and quantify changes in the ubiquitinated (Ub)-proteome during the aging process. More specifically, we compared wild-type worms at the first day of adulthood with young (day 5), mid-age (day 10) and aged adults (day 15). Moreover, we assessed protein levels of age-matched long-lived genetic models of dietary restriction (eat-2(ad1116)) and reduced insulin/IGF-1 signaling (daf-2(e1370)).

2021-05-26 | PXD025128 | Pride

Glucose Shortens the Lifespan of Caenorhabditis elegans by Down-Regulating Aquaporin Gene Expression

Project description:Many studies have addressed the effect of dietary glycemic index on obesity and diabetes, but little is known about its effect on lifespan itself. We found that adding a small amount of glucose to the medium (0.1-2%) shortened the lifespan of C. elegans. Glucose shortened lifespan by inhibiting the activities of lifespan-extending transcription factors that are also inhibited by insulin signaling: the FOXO family member DAF-16 and the heat shock factor HSF-1. This effect involved the down-regulation of an aquaporin glycerol channel, aqp-1. We show that changes in glycerol metabolism are likely to underlie the lifespan-shortening effect of glucose, and that aqp-1 may act cell non-autonomously as a feedback regulator in the insulin/IGF-1 signaling pathway. Insulin down-regulates similar glycerol channels in mammals, suggesting that this glucose-responsive pathway might be conserved evolutionarily. Together these findings raise the possibility that a low-sugar diet might have beneficial effects on lifespan in higher organisms. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE18561: Adult C. elegans: Control daf-2 mutants treated with daf-16 RNAi vs. daf-2 mutants treated with empty vector RNAi GSE18562: Adult C. elegans: Control OP50 culture vs. OP50 + 2% glucose culture

2010-05-16 | E-GEOD-18563 | biostudies-arrayexpress

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