Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions

2021 ◽  
Vol 118 (41) ◽  
pp. e2104832118
Author(s):  
Vinod K. Mony ◽  
Anna Drangowska-Way ◽  
Reka Albert ◽  
Emma Harrison ◽  
Abbas Ghaddar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Target Gene ◽  
Specific Nature ◽  
C Elegans ◽  
Functional Interactions ◽  
Genetic Epistasis ◽  
Specific Regulation ◽  
Context Specific ◽  
Factor Interactions ◽  
Multicellular Organisms

Plasticity in multicellular organisms involves signaling pathways converting contexts—either natural environmental challenges or laboratory perturbations—into context-specific changes in gene expression. Congruently, the interactions between the signaling molecules and transcription factors (TF) regulating these responses are also context specific. However, when a target gene responds across contexts, the upstream TF identified in one context is often inferred to regulate it across contexts. Reconciling these stable TF–target gene pair inferences with the context-specific nature of homeostatic responses is therefore needed. The induction of the Caenorhabditis elegans genes lipl-3 and lipl-4 is observed in many genetic contexts and is essential to survival during fasting. We find DAF-16/FOXO mediating lipl-4 induction in all contexts tested; hence, lipl-4 regulation seems context independent and compatible with across-context inferences. In contrast, DAF-16–mediated regulation of lipl-3 is context specific. DAF-16 reduces the induction of lipl-3 during fasting, yet it promotes it during oxidative stress. Through discrete dynamic modeling and genetic epistasis, we define that DAF-16 represses HLH-30/TFEB—the main TF activating lipl-3 during fasting. Contrastingly, DAF-16 activates the stress-responsive TF HSF-1 during oxidative stress, which promotes C. elegans survival through induction of lipl-3. Furthermore, the TF MXL-3 contributes to the dominance of HSF-1 at the expense of HLH-30 during oxidative stress but not during fasting. This study shows how context-specific diverting of functional interactions within a molecular network allows cells to specifically respond to a large number of contexts with a limited number of molecular players, a mode of transcriptional regulation we name “contextualized transcription.”

scholarly journals Context-Specific Regulation of NF-κB Target Gene Expression by EZH2 in Breast Cancers

2011 ◽  
Vol 43 (5) ◽  
pp. 798-810 ◽  
Author(s):  
Shuet Theng Lee ◽  
Zhimei Li ◽  
Zhenlong Wu ◽  
Meiyee Aau ◽  
Peiyong Guan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Breast Cancers ◽  
Target Gene Expression ◽  
Specific Regulation ◽  
Context Specific

scholarly journals The heat shock transcription factor HSF-1 protects Caenorhabditis elegans from peroxide stress

2020 ◽  
Author(s):  
Francesco A. Servello ◽  
Javier Apfeld
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Defense Mechanisms ◽  
Heat Shock Transcription Factor ◽  
Transactivation Domain ◽  
C Elegans ◽  
Multicellular Organisms ◽  
Mild Temperature

AbstractCells induce conserved defense mechanisms that protect them from oxidative stress. How these defenses are regulated in multicellular organisms is incompletely understood. Using the nematode Caenorhabditis elegans, we show that the heat shock transcription factor HSF-1 protects the nematode from the oxidative stress induced by environmental peroxide. In response to a heat shock or a mild temperature increase, HSF-1 protects the nematodes from subsequent oxidative stress in a manner that depends on HSF-1’s transactivation domain. At constant temperature, HSF-1 protects the nematodes from oxidative stress independently of its transactivation domain, likely by inducing the expression of asp-4/cathepsin D and dapk-1/dapk. Thus, two distinct HSF-1-dependent processes protect C. elegans from oxidative stress.

The Naturally Occurring ∆40p53 Isoform Inhibits eRNA Transcription and Enables Context-Specific Regulation During p53 Activation

2020 ◽  
Author(s):  
Cecilia Blair Levandowski ◽  
T. Jones ◽  
Margaret Gruca ◽  
Sivapriya Ramamoorthy ◽  
Robin Dowell ◽  
...  
Keyword(s):  
Naturally Occurring ◽  
P53 Activation ◽  
Specific Regulation ◽  
Context Specific

scholarly journals The secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenjing Qi ◽  
Erika D. V. Gromoff ◽  
Fan Xu ◽  
Qian Zhao ◽  
Wei Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Small Rnas ◽  
C Elegans ◽  
Cleavage Activity ◽  
Response To Temperature ◽  
Multicellular Organisms ◽  
Cell Immortality ◽  
Mature Mrnas ◽  
Endoribonuclease Activity

AbstractMulticellular organisms coordinate tissue specific responses to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, recent reports implicated release of small RNAs in regulating gene expression across tissue boundaries. Here, we show that the conserved poly-U specific endoribonuclease ENDU-2 in C. elegans is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 regulates gene expression across tissue boundaries in response to temperature alterations and contributes to maintenance of stem cell immortality, probably via retaining a stem cell specific program of gene expression.

Streblus asper Lour. exerts MAPK and SKN-1 mediated anti-aging, anti-photoaging activities and imparts neuroprotection by ameliorating Aβ in Caenorhabditis elegans

2021 ◽  
pp. 1-17
Author(s):  
Mani Iyer Prasanth ◽  
James Michael Brimson ◽  
Dicson Sheeja Malar ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Vital Role ◽  
Transgenic Strain ◽  
Wild Type ◽  
Neuroprotective Effects ◽  
C Elegans ◽  
Streblus Asper

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.

scholarly journals XBP1-Mediated BiP/GRP78 Upregulation Copes with Oxidative Stress in Mosquito Cells during Dengue 2 Virus Infection

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Tien-Huang Chen ◽  
Yi-Hsuan Chiang ◽  
Jiun-Nan Hou ◽  
Chih-Chieh Cheng ◽  
Eny Sofiyatun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Target Gene ◽  
Cytosolic Calcium ◽  
Cellular Damage ◽  
Factor X ◽  
Stress Indicators ◽  
Mosquito Cells ◽  
Tropical Areas ◽  
Oxidative Stress Indicators ◽  
Denv2 Infection

Dengue viruses (DENVs) cause dengue fever which is an important mosquito-borne disease in tropical areas. Generally, DENV does not cause cellular damage in mosquito cells. However, alterations in cytosolic calcium ions ([Ca2+]cyt) and the mitochondrial membrane potential (MMP), as well as accumulated reactive oxygen species (ROS), including superoxide anions (O2∙-) and hydrogen peroxide (H2O2), can be detected in C6/36 cells with DENV2 infection. Evident upregulation of BiP/GRP78 also appeared at 24 h postinfection in DENV2-infected C6/36 cells. As expression of BiP/GRP78 mRNA was reduced when the transcription factor X-box-binding protein-1 (XBP1) was knocked down in C6/36 cells, it demonstrated that BiP/GRP78 is the target gene regulated by the XBP1 signal pathway. We further demonstrated that the expression and splicing activity of XBP1 were upregulated in parallel with DENV2 infection in C6/36 cells. In C6/36 cells with BiP/GRP78 overexpression, oxidative stress indicators including [Ca2+]cyt, MMP,O2∙-, and H2O2were all pushed back to normal. Taken together, DENV2 activates XBP1 at earlier stage of infection, followed by upregulating BiP/GRP78 in mosquito cells. This regulatory pathway contributes a cascade in relation to oxidative stress alleviation. The finding provides insights into elucidating how mosquitoes can healthily serve as a vector of arboviruses in nature.

scholarly journals Crosstalk in oxygen homeostasis networks: SKN-1/NRF inhibits the HIF-1 hypoxia-inducible factor in Caenorhabditis elegans

2021 ◽  
Author(s):  
Dingxia Feng ◽  
Zhiwei Zhai ◽  
Zhiyong Shao ◽  
Yi Zhang ◽  
Jo Anne Powell-Coffman
Keyword(s):  
Oxidative Stress ◽  
Hypoxia Inducible Factor ◽  
Regulatory Sequences ◽  
Low Oxygen ◽  
Transcriptional Responses ◽  
C Elegans ◽  
Protein Levels ◽  
Oxygen Homeostasis ◽  
Genome Wide ◽  
A Genome

AbstractDuring development, homeostasis, and disease, organisms must balance responses that allow adaptation to low oxygen (hypoxia) with those that protect cells from oxidative stress. The evolutionarily conserved hypoxia-inducible factors are central to these processes, as they orchestrate transcriptional responses to oxygen deprivation. Here, we employ genetic strategies in C. elegans to identify stress-responsive genes and pathways that modulate the HIF-1 hypoxia-inducible factor and facilitate oxygen homeostasis. Through a genome-wide RNAi screen, we show that RNAi-mediated mitochondrial or proteasomal dysfunction increases the expression of hypoxia-responsive reporter Pnhr-57:GFP in C. elegans. Interestingly, only a subset of these effects requires hif-1. Of particular importance, we found that skn-1 RNAi increases the expression of hypoxia-responsive reporter Pnhr-57:GFP and elevates HIF-1 protein levels. The SKN-1/NRF transcription factor has been shown to promote oxidative stress resistance. We present evidence that the crosstalk between HIF-1 and SKN-1 is mediated by EGL-9, the prolyl hydroxylase that targets HIF-1 for oxygen-dependent degradation. Treatment that induces SKN-1, such as heat, increases expression of a Pegl-9:GFP reporter, and this effect requires skn-1 function and a putative SKN-1 binding site in egl-9 regulatory sequences. Collectively, these data support a model in which SKN-1 promotes egl-9 transcription, thereby inhibiting HIF-1. We propose that this interaction enables animals to adapt quickly to changes in cellular oxygenation and to better survive accompanying oxidative stress.

Phosphosite-specific regulation of the oxidative-stress response of Paracoccidioides brasiliensis: a shotgun phosphoproteomic analysis

2017 ◽  
Vol 19 (1) ◽  
pp. 34-46 ◽  
Author(s):  
Alison F.A. Chaves ◽  
Daniele G. Castilho ◽  
Marina V. Navarro ◽  
Ana K. Oliveira ◽  
Solange M.T. Serrano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Paracoccidioides Brasiliensis ◽  
Oxidative Stress Response ◽  
Specific Regulation

Regulation of a dpp target gene in the Drosophila embryo

Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 303-311 ◽  
Author(s):  
J. Rusch ◽  
M. Levine
Keyword(s):  
Target Gene ◽  
Fusion Gene ◽  
Drosophila Embryo ◽  
Specific Expression ◽  
Downstream Target ◽  
Embryonic Tissues ◽  
Posterior Midgut ◽  
Downstream Target Gene ◽  
Genetic Epistasis ◽  
Vp16 Fusion

In Drosophila, two TGF-beta growth factors, dpp and screw, function synergistically to subdivide the dorsal ectoderm into two embryonic tissues, the amnioserosa and dorsal epidermis. Previous studies have shown that peak dpp activity is required for the localized expression of zerknullt (zen), which encodes a homeodomain transcription factor. We present evidence that zen directly activates the amnioserosa-specific expression of a downstream target gene, Race (Related to angiotensin converting enzyme). A 533 bp enhancer from the Race promoter region is shown to mediate selective expression in the amnioserosa, as well as the anterior and posterior midgut rudiments. This enhancer contains three zen protein binding sites, and mutations in these sites virtually abolish the expression of an otherwise normal Race-lacZ fusion gene in the amnioserosa, but not in the gut. Genetic epistasis experiments suggest that zen is not the sole activator of Race, although a hyperactivated form of zen (a zen-VP16 fusion protein) can partially complement reduced levels of dpp activity. These results suggest that dpp regulates multiple transcription factors, which function synergistically to specify the amnioserosa.

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