Transcriptome analysis of mouse embrynic fibroblast cells lacking multiple core clock genes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE157946 | GEO | 2020/11/30
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptome analysis of mouse embrynic fibroblast cells lacking multiple core clock genes
| PRJNA663470 | ENA
Project description:The circadian system regulates numerous physiological processes including the adaptive immune system. Here we show that mice deficient for the circadian genes Cry1 and Cry2, (DKO) display an autoimmune phenotype including higher serum IgG concentration, presence of serum anti-nuclear antibodies, precipitation of IgG, IgM and complement 3 in glomeruli, and massive infiltrations of leukocytes into the lung and kidney. Activation of Cry DKO splenic B cells elicited markedly enhanced and prolonged tyrosine phosphorylation of cellular proteins compared to cells from control mice, suggesting that over activation of the BCR signaling pathway may contribute to autoimmunity in the Cry DKO mice. Expression of C1q, deficiency of which contributes to the pathogenesis of Systemic lupus erythematosus (SLE), was significantly downregulated in Cry DKO B cells. This suggests that B cell development, BCR signaling pathway and C1q expression may be under direct circadian control and dysregulation of which contributes to autoimmunity.
2018-08-24 | GSE87467 | GEO
Project description:Molecular analysis of circadian rhythm in mice. Liver tissue of wildtype, Clock mutant and Cry deficient C57BL/6 8- to 10-week-old male mice examined.
2007-11-07 | E-GEOD-454 | biostudies-arrayexpress
Project description:Molecular analysis of circadian rhythm in mice. Liver tissue of wildtype, Clock mutant and Cry deficient C57BL/6 8- to 10-week-old male mice examined. Keywords = circadian rhythm Keywords: other
2003-11-08 | GSE454 | GEO
Project description:The transcription-translation feedback loop, the core clock mechanism, is required for circadian rhythm. CRY protein, including CRY1 and CRY2, plays an important repressor role in the regulation of clock genes. However, other proteins, like PER1, PER2, NR1D1 and NR1D2, in the loop mask the transcriptional effects of CRY. This study provides data to find candidate genes specifically affected by CRY1 or CRY2 in mouse embryonic fibroblast (MEF) cells.
2024-02-21 | GSE246853 | GEO
Project description:By gating cell cycle progression to specific times of the day, the intracellular circadian clock is thought to reduce the exposure of replicating cells to potentially hazardous environmental and endogenous genotoxic compounds. Although core clock gene defects that eradicate circadian rhythmicity can cause an altered in vivo genotoxic stress response and aberrant proliferation rate, it remains to be determined to what extent these cell-cycle-related phenotypes are due to a cell-autonomous lack of circadian oscillations. We investigated the DNA damage sensitivity and proliferative capacity of cultured primary Cry1-/-|Cry2-/- fibroblasts. Contrasting previous in vivo studies, we show that the absence of CRY proteins does not affect the cell-autonomous DNA damage response upon exposure of primary cells in vitro to genotoxic agents, but causes cells to proliferate faster. By comparing primary wild type, Cry1-/-|Cry2-/-, Cry1+/-|Cry2-/- and Cry1-/-|Cry2+/- fibroblasts, we provide evidence that CRY proteins influence cell cycle progression in a cell-autonomous, but circadian clock-independent manner and that the accelerated cell cycle progression of Cry-deficient cells is caused by global dysregulation of Bmal1-dependent gene expression. These results suggest that the inconsistency between in vivo and in vitro observations might be attributed to systemic circadian control rather than a direct cell-autonomous control. Asynchronous proliferating MEFs grown under low (3%) oxygen tension and lysed in Trizol. Four independent cell lines were used for each genotype (WT, Cry DKO).
2011-09-30 | E-GEOD-31958 | biostudies-arrayexpress
Project description:The daily organisation of most mammalian cellular functions is attributed to circadian regulation of clock-controlled protein expression, driven by daily cycles of CRYPTOCHROME-dependent transcriptional feedback repression. To test this, we used quantitative mass spectrometry to compare wild type and CRY-deficient fibroblasts under constant conditions. In CRY-deficient cells, we found that temporal variation in protein, phosphopeptide, and K+ abundance was at least as great as wild type controls. Most strikingly. the extent of temporal variation within either genotype was much smaller than overall differences in proteome composition between WT and CRY-deficient cells. This proteome imbalance in CRY-deficient cells and tissues was associated with increased susceptibility to proteotoxic stress, which impairs circadian robustness, and may contribute to the wide-ranging phenotypes of CRY-deficient mice. Rather than generating largescale daily variation in proteome composition, we suggest it is plausible that the various transcriptional and post-translational functions of CRY proteins ultimately act to promote protein and osmotic homeostasis against daily perturbation.
2021-11-19 | PXD019499 | Pride
Project description:Circadian clocks are the time-keeping cellular apparatuses that are photoentrained according to the day-night photocycles on Earth 1,2. Cryptochromes (CRYs) are photoreceptors mediating photoentrainment of the circadian clock in plants and animals but how CRYs mediate light regulation of the molecular clock remains unclear 1,3. Here we show that CRYs mediate photoresponses of the circadian clock by regulating the activity of N6-methyladenosine (m6A) RNA methyltransferase and photoresponses of the epitranscriptome. In contrast to the presently known CRY complexome, the CRY2-methyltransferase complex exbibits multivalent interactions and photoresponsive condensation in response to blue light. We show that photoexcited CRY2 undergoes phosphorylation-assisted demixing to form photobodies with the properties of condensed liquid phase, which facilitates assembly of the CRY2-methyltransferase complex in the condensed liquid phase of CRY2 in vivo. The mta mutant impaired in m6A methyltransferase and the cry1cry2 mutant missing CRY photoreceptors share common defects of lengthened circadian period, reduced m6A RNA methylation, and accelerated degradation of mRNAs encoding core components of the molecular clock. These results argue for a photoentrainment mechanism by which blue light elicits liquid-liquid phase separation of the CRY2-methyltransferase complex to regulate m6A mRNA methylation, consequently suppressing mRNA degradation and period lengthening of the circadian clock
2021-07-12 | GSE152464 | GEO
Project description:Circadian clocks are the time-keeping cellular apparatuses that are photoentrained according to the day-night photocycles on Earth 1,2. Cryptochromes (CRYs) are photoreceptors mediating photoentrainment of the circadian clock in plants and animals but how CRYs mediate light regulation of the molecular clock remains unclear 1,3. Here we show that CRYs mediate photoresponses of the circadian clock by regulating the activity of N6-methyladenosine (m6A) RNA methyltransferase and photoresponses of the epitranscriptome. In contrast to the presently known CRY complexome, the CRY2-methyltransferase complex exbibits multivalent interactions and photoresponsive condensation in response to blue light. We show that photoexcited CRY2 undergoes phosphorylation-assisted demixing to form photobodies with the properties of condensed liquid phase, which facilitates assembly of the CRY2-methyltransferase complex in the condensed liquid phase of CRY2 in vivo. The mta mutant impaired in m6A methyltransferase and the cry1cry2 mutant missing CRY photoreceptors share common defects of lengthened circadian period, reduced m6A RNA methylation, and accelerated degradation of mRNAs encoding core components of the molecular clock. These results argue for a photoentrainment mechanism by which blue light elicits liquid-liquid phase separation of the CRY2-methyltransferase complex to regulate m6A mRNA methylation, consequently suppressing mRNA degradation and period lengthening of the circadian clock
2021-07-12 | GSE152465 | GEO
Project description:A new site of methylation was identified on histone H3 K42 in Saccharomyces cerevisiae. Mutations were engineered at this site to mimic either a constitutively modified state, K42L, or a constitutively unmodified state, K42Q in addition to an alanine substitution. K42A. The effects of these mutations on global transcription was monitored in yeast cells whose sole source of histone H3 was from a plasmid expressing these mutant proteins, and compared to that of an isogenic strain expressing the wild-type histone H3 protein from the same plasmid. Two biological replicates are included for each yeast strains expressing a specific histone H3 mutant. Three reference strains were also analyzed in the same way which expressed the wild-type histone protein. All strains were handled in the same way. A fresh culture of each strain was inoculated from a saturated overnight culture and grown to an OD A600 of approximately 0.7. Cells were harvested and total RNA extracted.
2010-05-27 | E-GEOD-13889 | biostudies-arrayexpress