UV-protection timer controls a trade-off between skin protection systems
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA472584 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tanning is a skin protection mechanism against UV radiation. Pigment production initiates hours after exposure, and the mechanism controlling this delay was unknown. Here we reveal a skin UV-protection timer, governed by damped oscillatory dynamics of the melanocyte master regulator, MITF, which after UV exposure, synchronizes regulatory programs, first cell survival and later pigmentation. Remarkably, the same amount of UV dosage resulted in higher pigmentation of human skin when given every-other day compared to daily exposure. Daily UV exposure appears to perturb MITF dynamics, thus re-ordering the survival and pigmentation programs. This demonstrates that the skin is more sensitive to frequency than quantity of UV exposure. Mathematical modeling identified a double negative regulatory loop involving HIF1a and microRNA-148a that regulates MITF dynamics. Our study suggests evolutionary leverage of the UV-protection timer, as it evolved to induce maximum protection with minimum damage for the reduction of skin cancer risk.
2018-10-26 | GSE114764 | GEO
Project description:Skin sun exposure induces two protection programs: stress responses and pigmentation, the former within minutes and the latter only hours afterward. Although serving the same physiological purpose, it is not known whether and how these programs are coordinated. Here, we report that UVB exposure every other day induces significantly more skin pigmentation than the higher frequency of daily exposure, without an associated increase in stress responses. Using mathematical modeling and empirical studies, we show that the melanocyte master regulator, MITF, serves to synchronize stress responses and pigmentation and, furthermore, functions as a UV-protection timer via damped oscillatory dynamics, thereby conferring a trade-off between the two programs. MITF oscillations are controlled by multiple negative regulatory loops, one at the transcriptional level involving HIF1α and another post-transcriptional loop involving microRNA-148a. These findings support trait linkage between the two skin protection programs, which, we speculate, arose during furless skin evolution to minimize skin damage.
| S-EPMC6224604 | biostudies-literature
Project description:We grouped Foxp3+ cells from Foxp3 Timer reporter mice into Blue1, Blue2, Red1, and Red2, and sorted these cells according to their Timer fluorescence expression, and analysed the transcriptional profiles of those cells, comparing them with those of effector and naive T cells using RNA-seq. Foxp3 Timer reporter mice were sensitised by a hapten, and 5 days later, the draining LNs of the skin were analysed.
2018-07-10 | GSE89481 | GEO
Project description:Exploring molecular details of carbon utilization trade-offs in galactose-evolved yeast Adaptively evolved yeast mutants on galactose for around 400 generations showed diminished growth and carbon uptake rates on glucose. Genome-scale approaches were applied to characterize the molecular genetic basis of these trade-offs in carbon source utilization. Engineered mutants showing trade-offs in a specific carbon uptake rate between both carbons were used as controls. The transcriptional responses of the evolved mutants were almost identical during growth on both carbon sources. These carbon-independent conserved patterns were clearly observed in specific pathways and genes. Up-regulation of PGM2, a confirmed beneficial genetic change for improving galactose utilization was preserved on both carbons. In addition, HXK1, GLK1 and genes involved in reserve carbohydrate metabolism were up-regulated, while HXK2 was down-regulated. Genes that have a transcription factor binding site for Gis1p, Rph1p, Msn2/4p and Nrg1p were up-regulated. These results indicated changes in the metabolic pathways involved in metabolism of both carbons and in nutrient signaling pathway. The concentration profile of trehalose and glycogen supported these findings. Mutations in RAS2 and ERG5 genes were selected because of their beneficial and neutral effect on galactose utilization, respectively in our previous study. Site-directed mutants containing galactose-beneficial mutations in RAS2 only resulted in a significant decrease in glucose utilization. Integration of all these analyses clearly suggest an antagonistic pleiotropic trade-off in carbon source utilization caused by changes in regulatory region, and we hereby demonstrate how systems biology can be used to gain insight into evolutionary processes at the molecular level. Yeast galactose evolved mutants having improved galactose availability were grown on aerobic batch with glucose as carbon source
2012-07-31 | E-GEOD-39065 | biostudies-arrayexpress
Project description:Type 1 interferon (IFN) plays a critical role in early antiviral defense and priming of adaptive immunity by signalling upregulation of host antiviral interferon-stimulated genes (ISGs). Certain stimuli trigger strong activation of IFN regulatory factor 3 (IRF3) and direct upregulation of ISGs in addition to IFN. It remains unclear why some stimuli are stronger activators of IRF3 and how this leads to IFN-independent antiviral protection. We found that UV-inactivated human cytomegalovirus (HCMV) particles triggered an IFN-independent ISG signature that was absent in cells infected with UV-inactivated Sendai virus (SeV) particles. HCMV particles triggered mostly uniform activation of IRF3 and low-level IFN-? production within the population while SeV particles triggered a small fraction of cells producing abundant IFN-?. These findings suggest that population level activation of IRF3 and antiviral protection emerges from a diversity of responses occurring simultaneously in single cells. Moreover, this occurs in the absence of virus replication.
2020-05-02 | GSE149705 | GEO
Project description:Zygotic genome activation (ZGA) is a complex process which denotes the initiation of gene expression after fertilization. Deciphering the proper timing and genes involved in ZGA program is still a fundamental challenge in early embryo development. Here, we present a new ZGA gene identification framework, named ZGA-Timer, based on the timecourse pattern from RNA-seq data. By performing ZGA-Timer and siRNA technology, we confirmed Uqcc3 as a novel ZGA gene in mice. As a unique feature of ZGA-Timer, time-series RNA-seq data are modeled by a pattern recognition method and the onset of ZGA can be estimated in multiple species. ZGA-Timer outperforms current foldchange-based approaches. Furthermore, we investigate the epigenetic modifications and find that accessible chromatin predominately contributes to the regulation of ZGA genes. Moreover, ZGA genes show significant enrichment in housekeeping genes and cancer driver genes. Together, our ZGA-Timer framework provides a new approach to further understand the ZGA process.
2021-05-18 | GSE174530 | GEO
Project description:This project was conducted by Nitin S. Baliga of the Halobacterium group at the Institute for Systems Biology in collaboration with Jocelyne Diruggiero of University of Maryland. Halobacterium NRC-1 cell pellets were resuspended in an isotonic buffer at a low density, placed on ice and exposed to 200J/m2 of UV-C irradiation, returned to the growth medium and allowed to recover at 42oC in dark (D) or light (L). Total RNA was collected from each sample at 30 minutes (D30 and L30) and 60 minutes (L60 and D60). The control (C) was processed in a manner to identical to L60 except that it did not suffer any UV-C insult. The reference RNA was prepared from an aliquot of the same culture just prior to UV-C irradiation. Therefore the reference was also exposed to initial perturbations prior to UV-C irradiation such as change of growth medium to buffer and change of temperature from 42oC to ice. Keywords = ISB Keywords = Halobacterium NRC-1 Keywords = UV repair Keywords = ultraviolet radiation Keywords = stress response Keywords: other
2004-02-14 | GSE1040 | GEO
Project description:In plants, ultraviolet (UV)-light is an important driver for their growth and natural distribution and is also a valuable tool for manipulating their productivity as well as their biotic interactions. Understanding plant responses to different UV radiation is sparse, especially from a systems biology perspective and particularly for conifers. Here, we evaluated the physiological and transcriptomic responses to the short-term application of high-irradiance UV-B and UV-C waves on Pinus tabuliformis Carr., a major conifer in Northern China. By undertaking time-ordered gene co-expression network analyses and network comparisons incorporating physiological traits and gene expression variation, we uncovered communalities but also differences in P. tabuliformis responses to UV-B and UV-C. Both types of spectral bands caused a significant inhibition of photosynthesis and conversely improvement of antioxidant capacity, flavonoid production and signaling pathways related to stress resistance, indicating a clear switch from predominantly primary metabolism to enhanced defensive metabolism in pine. We isolated distinct subnetworks for photoreceptor-mediated signal transduction, maximum quantum efficiency of photosystem II (Fv/Fm) regulation and flavonoid biosynthesis in response to UV-B and UV-C irradiation. From these subnetworks, we further identified phototropins as potential important elements in both UV-B and UV-C signaling and, for the first time, reveal peptide hormones possibly involved in promoting flavonoid biosynthesis against UV-B, while these hormones seem not to be implicated in defense against UV-C exposure. The present study employed an effective strategy for disentangling the complex physiological and genetic regulatory mechanisms in a non-model plant species, and thus, provides a suitable reference for future functional evaluations and artificial UV-light mediated growing strategies in plant production.
2022-10-10 | GSE185987 | GEO
Project description:Ouyang2014 - photomorphogenic UV-B signalling
network
This model is described in the article:
Coordinated photomorphogenic
UV-B signaling network captured by mathematical modeling.
Ouyang X, Huang X, Jin X, Chen Z,
Yang P, Ge H, Li S, Deng XW.
Proc. Natl. Acad. Sci. U.S.A. 2014 Aug;
111(31): 11539-11544
Abstract:
Long-wavelength and low-fluence UV-B light is an
informational signal known to induce photomorphogenic
development in plants. Using the model plant Arabidopsis
thaliana, a variety of factors involved in UV-B-specific
signaling have been experimentally characterized over the past
decade, including the UV-B light receptor UV resistance locus
8; the positive regulators constitutive photomorphogenesis 1
and elongated hypocotyl 5; and the negative regulators cullin4,
repressor of UV-B photomorphogenesis 1 (RUP1), and RUP2.
Individual genetic and molecular studies have revealed that
these proteins function in either positive or negative
regulatory capacities for the sufficient and balanced
transduction of photomorphogenic UV-B signal. Less is known,
however, regarding how these signaling events are
systematically linked. In our study, we use a systems biology
approach to investigate the dynamic behaviors and correlations
of multiple signaling components involved in Arabidopsis
UV-B-induced photomorphogenesis. We define a mathematical
representation of photomorphogenic UV-B signaling at a temporal
scale. Supplemented with experimental validation, our
computational modeling demonstrates the functional interaction
that occurs among different protein complexes in early and
prolonged response to photomorphogenic UV-B.
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2024-09-02 | BIOMD0000000545 | BioModels
Project description:Exploring molecular details of carbon utilization trade-offs in galactose-evolved yeast Adaptively evolved yeast mutants on galactose for around 400 generations showed diminished growth and carbon uptake rates on glucose. Genome-scale approaches were applied to characterize the molecular genetic basis of these trade-offs in carbon source utilization. Engineered mutants showing trade-offs in a specific carbon uptake rate between both carbons were used as controls. The transcriptional responses of the evolved mutants were almost identical during growth on both carbon sources. These carbon-independent conserved patterns were clearly observed in specific pathways and genes. Up-regulation of PGM2, a confirmed beneficial genetic change for improving galactose utilization was preserved on both carbons. In addition, HXK1, GLK1 and genes involved in reserve carbohydrate metabolism were up-regulated, while HXK2 was down-regulated. Genes that have a transcription factor binding site for Gis1p, Rph1p, Msn2/4p and Nrg1p were up-regulated. These results indicated changes in the metabolic pathways involved in metabolism of both carbons and in nutrient signaling pathway. The concentration profile of trehalose and glycogen supported these findings. Mutations in RAS2 and ERG5 genes were selected because of their beneficial and neutral effect on galactose utilization, respectively in our previous study. Site-directed mutants containing galactose-beneficial mutations in RAS2 only resulted in a significant decrease in glucose utilization. Integration of all these analyses clearly suggest an antagonistic pleiotropic trade-off in carbon source utilization caused by changes in regulatory region, and we hereby demonstrate how systems biology can be used to gain insight into evolutionary processes at the molecular level.
2012-08-01 | GSE39065 | GEO