Nuclear receptor signal transduction in C. elegans

Antebi, Adam

doi:10.1895/wormbook.1.64.2

Cited by 80 publications

(88 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, the functions of daf-12 appear to be more conserved with EcR than its apparent fly and vertebrate orthologs, all of which function in lipid metabolism. In both flies and insects, insulin signaling and TGFβ signaling converge with the production of a lipophilic hormone that binds EcR (in the fly) or DAF-12 (in the worm), both of which regulate the let-7 miRNA that in turn mediates major life cycle transitions [89,90]. Interestingly, this pathway may also have a vertebrate analog, whereby estrogen signaling activates the transition to puberty via Estrogen Receptor.…”

Section: Hr96/daf-12/vdr/pxr/car (Nr1ij)mentioning

confidence: 99%

See 1 more Smart Citation

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

Bodofsky¹,

Koitz²,

Wightman³

2017

Nuclear Receptor Research

View full text Add to dashboard Cite

The nuclear receptor gene family includes 18 members that are broadly conserved among multiple disparate animal phyla, indicating that they trace their evolutionary origins to the time at which animal life arose. Typical nuclear receptors contain two major domains: a DNA-binding domain and a C-terminal domain that may bind a lipophilic hormone. Many of these nuclear receptors play varied roles in animal development, including coordination of life cycle events and cellular differentiation. The well-studied genetic model systems of Drosophila, C. elegans, and mouse permit an evaluation of the extent to which nuclear receptor function in development is conserved or exapted (repurposed) over animal evolution. While there are some specific examples of conserved functions and pathways, there are many clear examples of exaptation. Overall, the evolutionary theme of exaptation appears to be favored over strict functional conservation. Despite strong conservation of DNA-binding domain sequences and activity, the nuclear receptors prove to be highly-flexible regulators of animal development.

show abstract

Section: Hr96/daf-12/vdr/pxr/car (Nr1ij)mentioning

confidence: 99%

“…While most of these nuclear receptors have not yet been functionally-characterized, of the dozen or so that have been studied most play some role in regulating metabolism, similar to flies and vertebrates [90]. This includes the well-characterized nuclear receptors nhr-13, -49, -63, -64, -66, -69, -76 , and -80 .…”

Section: Hnf4 (Nr2a)mentioning

confidence: 99%

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

Bodofsky¹,

Koitz²,

Wightman³

2017

Nuclear Receptor Research

View full text Add to dashboard Cite

show abstract

“…26 In C. elegans, the NHR family has expanded to include 284 members, many of which are derived from a single ancestor, the hepatocyte nuclear factor 4 (HNF4). 27,28 In a recent study, we identified a group of NHRs that are essential for the longevity of germline-ablated worms. Of these, NHR-49 produced the most striking lifespan phenotypes.…”

Section: Introductionmentioning

confidence: 99%

“…29,30 The degree of equivalence between NHR-49 and PPARa is currently unclear, but in view of their similar activities, and for clarity and convenience, NHR-49 is referred to as the functional homolog of PPARa, here and in other studies. 27,[31][32][33] PPARa is a key regulator of fatty-acid b-oxidation and a member of the PPAR family that also includes other modulators of energy metabolism. 34 nhr-49 was first identified as a regulator of mitochondrial b-oxidation genes during development and for inducing the expression of some b-oxidation while repressing others during short-term fasting.…”

Section: Introductionmentioning

confidence: 99%

“…22 nhr-49 mutants exhibit altered expression of enzymes that mediate fatty-acid desaturation, during development as well as fasting. 29,30 Fatty-acid desaturation is also regulated by NHR-80 that is structurally similar to HNF4 37 (we refer to NHR-80 as NHR-80/HNF4 in keeping with the terminology used in worm literature 21,27 ). In a previous study, Hugo Aguilaniu's laboratory reported that, in germline-less mutants too, NHR-80/HNF4 elevates the expression of enzymes responsible for converting a saturated fatty acid (SFA), stearic acid (SA, C16:0) into a mono-unsaturated fatty acid (MUFA), oleic acid (OA, C18:1n9).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nuclear hormone receptors as mediators of metabolic adaptability following reproductive perturbations

Ratnappan

Ward

Ghazi

2016

Worm

View full text Add to dashboard Cite

Previously, we identified a group of nuclear hormone receptors (NHRs) that promote longevity in the nematode Caenorhabditis elegans following germline-stem cell (GSC) loss. This group included NHR-49, the worm protein that performs functions similar to vertebrate PPARa, a key regulator of lipid metabolism. We showed that NHR-49/PPARa enhances mitochondrial b-oxidation and fatty acid desaturation upon germline removal, and through the coordinated enhancement of these processes allows the animal to retain lipid homeostasis and undergo lifespan extension. NHR-49/ PPARa expression is elevated in GSC-ablated animals, in part, by DAF-16/FOXO3A and TCER-1/ TCERG1, two other conserved, pro-longevity transcriptional regulators that are essential for germline-less longevity. In exploring the roles of the other pro-longevity NHRs, we discovered that one of them, NHR-71/HNF4, physically interacted with NHR-49/PPARa. NHR-71/HNF4 did not have a broad impact on the expression of b-oxidation and desaturation targets of NHR-49/PPARa. But, both NHR-49/PPARa and NHR-71/HNF4 were essential for the increased expression of DAF-16/ FOXO3A-and TCER-1/TCERG1-downstream target genes. In addition, nhr-49 inactivation caused a striking membrane localization of KRI-1, the only known common upstream regulator of DAF-16/ FOXO3A and TCER-1/TCERG1, suggesting that it may operate in a positive feedback loop to potentiate the activity of this pathway. These data underscore how selective interactions between NHRs that function as nodes in metabolic networks, confer functional specificity in response to different physiological stimuli.

show abstract

Caenorhabditis elegans as an emerging model system in environmental epigenetics

Weinhouse

Truong

Meyer

et al. 2018

Environ and Mol Mutagen

View full text Add to dashboard Cite

The roundworm Caenorhabitis elegans has been an established model organism for the study of genetics and developmental biology, including studies of transcriptional regulation, since the 1970s. This model organism has continued to be used as a classical model system as the field of transcriptional regulation has expanded to include scientific advances in epigenetics and chromatin biology. In the last several decades, C. elegans has emerged as a powerful model for environmental toxicology, particularly for the study of chemical genotoxicity. Here, we outline the utility and applicability of C. elegans as a powerful model organism for mechanistic studies of environmental influences on the epigenome. Our goal in this article is to inform the field of environmental epigenetics of the strengths and limitations of the well-established C. elegans model organism as an emerging model for medium-throughput, in vivo exploration of the role of exogenous chemical stimuli in transcriptional regulation, developmental epigenetic reprogramming, and epigenetic memory and inheritance. As the field of environmental epigenetics matures, and research begins to map mechanisms underlying observed associations, new toolkits and model systems, particularly manipulable, scalable in vivo systems that accurately model human transcriptional regulatory circuits, will provide an essential experimental bridge between in vitro biochemical experiments and mammalian model systems. Environ. Mol. Mutagen. 59:560-575, 2018. © 2018 Wiley Periodicals, Inc.

show abstract

Nuclear receptor signal transduction in C. elegans

Cited by 80 publications

References 25 publications

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

Nuclear hormone receptors as mediators of metabolic adaptability following reproductive perturbations

Caenorhabditis elegans as an emerging model system in environmental epigenetics

Contact Info

Product

Resources

About