UV-protection timer controls a trade-off between skin protection systems
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ABSTRACT:
PROVIDER: PRJNA472584 | ENA |
REPOSITORIES: ENA
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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.
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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
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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
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Project description:Oryza sativa Japonica Group UV-DDB1, UV-damaged DNA binding protein, is differentially expressed in 15 experiment(s);
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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.
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