scholarly journals Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks

2021 ◽  
Author(s):  
Michal Dudek ◽  
Dharshika Pathiranage ◽  
Catia F Goncalves ◽  
Craig Lawless ◽  
Dong Wang ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
Clock Genes ◽  
Phase Relationship ◽  
Environmental Cues ◽  
Daily Rhythms ◽  
Rhythmic Expression ◽  
Diurnal Patterns ◽  
Genome Wide ◽  
Bona Fide ◽  
Osmotic Stimuli

In mammals, temporally coordinated daily rhythms of behaviour and physiology are generated by a multi-oscillatory circadian system, entrained through cyclic environmental cues (e.g. light). Presence of niche-dependent physiological time cues has been proposed, which would allow local tissues flexibility of adopting a different phase relationship if circumstances require. Up till now, such tissue-unique stimuli have remained elusive. Here we show that cycles of mechanical loading and osmotic stimuli within physiological range drive rhythmic expression of clock genes and reset clock phase and amplitude in cartilage and intervertebral disc tissues. Hyperosmolarity (and not hypo-osmolarity) resets clocks in young and ageing skeletal tissues through mTORC2-AKT-GSK3β pathway, leading to genome-wide induction of rhythmic genes. These results suggest diurnal patterns of mechanical loading and consequent daily surges in extracellular osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.

scholarly journals Clock Gene Expression in Adult Primate Suprachiasmatic Nuclei and Adrenal: Is the Adrenal a Peripheral Clock Responsive to Melatonin?

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1454-1461 ◽  
Author(s):  
F. J. Valenzuela ◽  
C. Torres-Farfan ◽  
H. G. Richter ◽  
N. Mendez ◽  
C. Campino ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Clock Gene ◽  
Clock Genes ◽  
Phase Relationship ◽  
Suprachiasmatic Nuclei ◽  
Rhythmic Expression ◽  
Peripheral Oscillators ◽  
Clock Gene Expression ◽  
Timing System ◽  
Circadian Timing System

The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000–0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400–2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3β-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nm melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.

scholarly journals Genome-wide correlation analysis to identify amplitude regulators of circadian transcriptome output

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Evan S. Littleton ◽  
Madison L. Childress ◽  
Michaela L. Gosting ◽  
Ayana N. Jackson ◽  
Shihoko Kojima
Keyword(s):  
Clock Genes ◽  
Circadian System ◽  
Average Level ◽  
Relative Amplitude ◽  
Critical Component ◽  
Period 2 ◽  
Genome Wide ◽  
Mouse Tissues ◽  
Rhythmic Gene ◽  
Insight Into

AbstractCell-autonomous circadian system, consisting of core clock genes, generates near 24-h rhythms and regulates the downstream rhythmic gene expression. While it has become clear that the percentage of rhythmic genes varies among mouse tissues, it remains unclear how this variation can be generated, particularly when the clock machinery is nearly identical in all tissues. In this study, we sought to characterize circadian transcriptome datasets that are publicly available and identify the critical component(s) involved in creating this variation. We found that the relative amplitude of 13 genes and the average level of 197 genes correlated with the percentage of cycling genes. Of those, the correlation of Rorc in both relative amplitude and the average level was one of the strongest. In addition, the level of Per2AS, a novel non-coding transcript that is expressed at the Period 2 locus, was also linearly correlated, although with a much lesser degree compared to Rorc. Overall, our study provides insight into how the variation in the percentage of clock-controlled genes can be generated in mouse tissues and suggests that Rorc and potentially Per2AS are involved in regulating the amplitude of circadian transcriptome output.

scholarly journals Nascent RNA sequencing identifies a widespread sigma70-dependent pausing regulated by Gre factors in bacteria

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhe Sun ◽  
Alexander V. Yakhnin ◽  
Peter C. FitzGerald ◽  
Carl E. Mclntosh ◽  
Mikhail Kashlev
Keyword(s):  
Environmental Cues ◽  
Start Site ◽  
Transcription Start ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Vitro Analysis ◽  
In Vitro Analysis

AbstractPromoter-proximal pausing regulates eukaryotic gene expression and serves as checkpoints to assemble elongation/splicing machinery. Little is known how broadly this type of pausing regulates transcription in bacteria. We apply nascent elongating transcript sequencing combined with RNase I footprinting for genome-wide analysis of σ70-dependent transcription pauses in Escherichia coli. Retention of σ70 induces strong backtracked pauses at a 10−20-bp distance from many promoters. The pauses in the 10−15-bp register of the promoter are dictated by the canonical −10 element, 6−7 nt spacer and “YR+1Y” motif centered at the transcription start site. The promoters for the pauses in the 16−20-bp register contain an additional −10-like sequence recognized by σ70. Our in vitro analysis reveals that DNA scrunching is involved in these pauses relieved by Gre cleavage factors. The genes coding for transcription factors are enriched in these pauses, suggesting that σ70 and Gre proteins regulate transcription in response to changing environmental cues.

Stability of the Synechococcus elongatus PCC 7942 circadian clock under directed anti-phase expression of the kai genes

Microbiology ◽  
2005 ◽  
Vol 151 (8) ◽  
pp. 2605-2613 ◽  
Author(s):  
Jayna L. Ditty ◽  
Shannon R. Canales ◽  
Breanne E. Anderson ◽  
Stanly B. Williams ◽  
Susan S. Golden
Keyword(s):  
Circadian Clock ◽  
Expression Patterns ◽  
Phase Relationship ◽  
Synechococcus Elongatus ◽  
Cycle Period ◽  
Rhythmic Expression ◽  
Core Components ◽  
Synechococcus Elongatus Pcc 7942 ◽  
Time Required ◽  
Pcc 7942

The kaiA, kaiB and kaiC genes encode the core components of the cyanobacterial circadian clock in Synechococcus elongatus PCC 7942. Rhythmic expression patterns of kaiA and of the kaiBC operon normally peak in synchrony. In some mutants the relative timing of peaks (phase relationship) between these transcription units is altered, but circadian rhythms persist robustly. In this study, the importance of the transcriptional timing of kai genes was examined. Expressing either kaiA or kaiBC from a heterologous promoter whose peak expression occurs 12 h out of phase from the norm, and thus 12 h out of phase from the other kai locus, did not affect the time required for one cycle (period) or phase of the circadian rhythm, as measured by bioluminescence reporters. Furthermore, the data confirm that specific cis elements within the promoters of the kai genes are not necessary to sustain clock function.

scholarly journals Daily rhythms in gene expression of the human parasite Schistosoma mansoni

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kate A. Rawlinson ◽  
Adam J. Reid ◽  
Zhigang Lu ◽  
Patrick Driguez ◽  
Anna Wawer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Schistosoma Mansoni ◽  
Circadian Clock ◽  
Drug Targets ◽  
Clock Genes ◽  
Biological Rhythms ◽  
Active Phase ◽  
Egg Laying ◽  
Daily Rhythms ◽  
Metazoan Parasites

Abstract Background The consequences of the earth’s daily rotation have led to 24-h biological rhythms in most organisms. Even some parasites are known to have daily rhythms, which, when in synchrony with host rhythms, can optimise their fitness. Understanding these rhythms may enable the development of control strategies that take advantage of rhythmic vulnerabilities. Recent work on protozoan parasites has revealed 24-h rhythms in gene expression, drug sensitivity and the presence of an intrinsic circadian clock; however, similar studies on metazoan parasites are lacking. To address this, we investigated if a metazoan parasite has daily molecular oscillations, whether they reveal how these longer-lived organisms can survive host daily cycles over a lifespan of many years and if animal circadian clock genes are present and rhythmic. We addressed these questions using the human blood fluke Schistosoma mansoni that lives in the vasculature for decades and causes the tropical disease schistosomiasis. Results Using round-the-clock transcriptomics of male and female adult worms collected from experimentally infected mice, we discovered that ~ 2% of its genes followed a daily pattern of expression. Rhythmic processes included a stress response during the host’s active phase and a ‘peak in metabolic activity’ during the host’s resting phase. Transcriptional profiles in the female reproductive system were mirrored by daily patterns in egg laying (eggs are the main drivers of the host pathology). Genes cycling with the highest amplitudes include predicted drug targets and a vaccine candidate. These 24-h rhythms may be driven by host rhythms and/or generated by a circadian clock; however, orthologs of core clock genes are missing and secondary clock genes show no 24-h rhythmicity. Conclusions There are daily rhythms in the transcriptomes of adult S. mansoni, but they appear less pronounced than in other organisms. The rhythms reveal temporally compartmentalised internal processes and host interactions relevant to within-host survival and between-host transmission. Our findings suggest that if these daily rhythms are generated by an intrinsic circadian clock then the oscillatory mechanism must be distinct from that in other animals. We have shown which transcripts oscillate at this temporal scale and this will benefit the development and delivery of treatments against schistosomiasis.

scholarly journals Low temperature triggers genome-wide hypermethylation of transposable elements and centromeres in maize

2019 ◽  
Author(s):  
Zeineb Achour ◽  
Johann Joets ◽  
Martine Leguilloux ◽  
Hélène Sellier ◽  
Jean-Philippe Pichon ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transposable Elements ◽  
Transcriptional Activation ◽  
Gene Expression Regulation ◽  
Environmental Cues ◽  
Specific Response ◽  
Genome Wide ◽  
A Genome ◽  
Response To Stress ◽  
Context Specific

ABSTRACTCharacterizing the molecular processes developed by plants to respond to environmental cues is a major task to better understand local adaptation. DNA methylation is a chromatin mark involved in the transcriptional silencing of transposable elements (TEs) and gene expression regulation. While the molecular bases of DNA methylation regulation are now well described, involvement of DNA methylation in plant response to environmental cues remains poorly characterized. Here, using the TE-rich maize genome and analyzing methylome response to prolonged cold at the chromosome and feature scales, we investigate how genomic architecture affects methylome response to stress in a cold-sensitive genotype. Interestingly, we show that cold stress induces a genome-wide methylation increase through the hypermethylation of TE sequences and centromeres. Our work highlights a cytosine context-specific response of TE methylation that depends on TE types, chromosomal location and proximity to genes. The patterns observed can be explained by the parallel transcriptional activation of multiple DNA methylation pathways that methylate TEs in the various chromatin locations where they reside. Our results open new insights into the possible role of genome-wide DNA methylation in phenotypic response to stress.

scholarly journals Chronic Corticosterone Disrupts the Circadian Rhythm of CRH Expression and M6a RNA Methylation in the Chicken Hypothalamus

2021 ◽  
Author(s):  
Yang Yang ◽  
Wanwan Han ◽  
Aijia Zhang ◽  
Mindie Zhao ◽  
Wei Cong ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Clock Genes ◽  
Diurnal Fluctuation ◽  
Opposite Pattern ◽  
Rna Methylation ◽  
Diurnal Patterns ◽  
M6a Rna Methylation

Abstract Corticotropin-releasing hormone (CRH), the major secretagogue of the hypothalamic-pituitary-adrenal (HPA) axis, is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions. N6-methyladenosine (m6A) RNA methylation is involved in the regulation of circadian rhythm, yet it remains unknown whether CRH expression and m6A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress. Here, we show that chronic exposure to corticosterone (CORT) eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken. The circadian rhythms of clock genes in hippocampus, hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens. The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened, together with mRNA of other feeding-related neuropeptides. Interestingly, hypothalamic m6A level oscillates in an opposite pattern to CRH mRNA, with lowest m6A level after midnight (ZT18) corresponding to the peak of CRH mRNA before dawn (ZT22). CORT diminished the circadian rhythm of m6A methylation with significantly increased level at night. Further site-specific m6A analysis on 3’UTR of CRH mRNA indicates that higher m6A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night (ZT18 and ZT22). Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus, leading to dysfunction of HPA axis in the chicken. RNA m6A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions.

scholarly journals Pregnancy-induced changes in the circadian expression of hepatic clock genes: implications for maternal glucose homeostasis

2016 ◽  
Vol 311 (3) ◽  
pp. E575-E586 ◽  
Author(s):  
Michaela D. Wharfe ◽  
Caitlin S. Wyrwoll ◽  
Brendan J. Waddell ◽  
Peter J. Mark
Keyword(s):  
Clock Genes ◽  
Circadian Variation ◽  
Late Gestation ◽  
Hepatic Expression ◽  
Rhythmic Expression ◽  
Circadian Expression ◽  
Clock Gene Expression ◽  
Maternal Adaptation ◽  
Near Term ◽  
In Pregnancy

Adaptations in maternal carbohydrate metabolism are particularly important in pregnancy because glucose is the principal energy substrate used by the fetus. As metabolic homeostasis is intricately linked to the circadian system via the rhythmic expression of clock genes, it is likely that metabolic adaptations during pregnancy also involve shifts in maternal circadian function. We hypothesized that maternal adaptation in pregnancy involves changes in the hepatic expression of clock genes, which drive downstream shifts in circadian expression of glucoregulatory genes. Maternal liver and plasma ( n = 6–8/group) were collected across 24-h periods (0800, 1200, 1600, 2000, 0000, 0400) from C57Bl/6J mice under isoflurane-nitrous oxide anesthesia prior to and on days 6, 10, 14 and 18 of pregnancy (term = day 19). Hepatic expression of clock genes and glucoregulatory genes was determined by RT-qPCR. Hepatic clock gene expression was substantially altered across pregnancy, most notably in late gestation when the circadian rhythmicity of several clock genes was attenuated (≤64% reduced amplitude on day 18). These changes were associated with a similar decline in rhythmicity of the key glucoregulatory genes Pck1, G6Pase, and Gk, and by day 18, Pck1 was no longer rhythmic. Overall, our data show marked adaptations in the liver clock during mouse pregnancy, changes that may contribute to the altered circadian variation in glucoregulatory genes near term. We propose that the observed reduction of daily oscillations in glucose metabolism ensure a sustained supply of glucose to meet the high demands of fetal growth.

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