The molecular basis of circadian rhythm, driven by core clock genes such as Per1/2, has been investigated on the transcriptome level, but not comprehensively on the proteome level. Here we quantified over 11,000 proteins expressed in eight types of tissues over 46 h with an interval of 2 h, using WT and Per1/Per2 double knockout mouse models. The multitissue circadian proteome landscape of WT mice shows tissue-specific patterns and reflects circadian anticipatory phenomena, which are less obvious on the transcript level. In most peripheral tissues of double knockout mice, reduced protein cyclers are identified when compared with those in WT mice. In addition, PER1/2 contributes to controlling the anticipation of the circadian rhythm, modulating tissue-specific cyclers as well as key pathways including nucleotide excision repair. Severe intertissue temporal dissonance of circadian proteome has been observed in the absence of Per1 and Per2. The γ-aminobutyric acid might modulate some of these temporally correlated cyclers in WT mice. Our study deepens our understanding of rhythmic proteins across multiple tissues and provides valuable insights into chronochemotherapy. The data are accessible at https://prot-rhythm.prottalks.com/.
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http://dx.doi.org/10.1016/j.mcpro.2023.100675 | DOI Listing |
Philos Trans R Soc Lond B Biol Sci
January 2025
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
The mammalian cryptochrome proteins (CRY1 and CRY2) are transcriptional repressors most notable for their role in circadian transcriptional feedback. Not all circadian rhythms depend on CRY proteins, however, and the CRY proteins are promiscuous interactors that also regulate many other processes. In cells with chronic CRY deficiency, protein homeostasis is highly perturbed, with a basal increase in cellular stress and activation of key inflammatory signalling pathways.
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
January 2025
Department of Infectious Disease, Imperial College London, London SW7 2AZ, UK.
The within-host environment changes over circadian time and influences the replication and severity of viruses. Genetic knockout of the circadian transcription factors CRYPTOCHROME 1 and CRYPTOCHROME 2 (/; CKO) leads to altered protein homeostasis and chronic activation of the integrated stress response (ISR). The adaptive ISR signalling pathways help restore cellular homeostasis by downregulating protein synthesis in response to endoplasmic reticulum overloading or viral infections.
View Article and Find Full Text PDFNature
January 2025
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.
View Article and Find Full Text PDFPlant Cell Environ
January 2025
Department of Biology, Trivedi School of Biosciences, Ashoka University, Sonipat, India.
Circadian clocks execute temporal regulation of metabolism by modulating the timely expression of genes. Clock regulation of mRNA synthesis was envisioned as the primary driver of these daily rhythms. mRNA oscillations often do not concur with the downstream protein oscillations, revealing the importance to study protein oscillations.
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