Cold induced chromatin compaction and nuclear retention of clock mRNAs resets the circadian rhythm

AbstractCooling patients to sub-physiological temperatures is an integral part of modern medicine. We show that cold exposure induces temperature-specific changes to the higher-order chromatin and gene expression profiles of human cells. These changes are particularly dramatic at 18°C, a temperature synonymous with that experienced by patients undergoing controlled deep-hypothermia during surgery. Cells exposed to 18°C exhibit largely nuclear-restricted transcriptome changes. These include the nuclear accumulation of core circadian clock suppressor gene transcripts, most notably REV-ERBα. This response is accompanied by compaction of higher-order chromatin and hindrance of mRNPs from engaging nuclear pores. Rewarming reverses chromatin compaction and releases the transcripts into the cytoplasm, triggering a pulse of suppressor gene proteins that resets the circadian clock. We show that cold-induced upregulation of REV-ERBα alone is sufficient to trigger this resetting. Our findings uncover principles of the cellular cold-response that must be considered for current and future applications involving therapeutic deep-hypothermia.

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Circadian clock and steroidogenic-related gene expression profiles in mouse Leydig cells following dexamethasone stimulation

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2016.12.149 ◽

2017 ◽

Vol 483 (1) ◽

pp. 294-300 ◽

Cited By ~ 11

Author(s):

Huatao Chen ◽

Lei Gao ◽

Yongjie Xiong ◽

Dan Yang ◽

Cuimei Li ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Leydig Cells ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Related Gene

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Development and entrainment of the colonic circadian clock during ontogenesis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00340.2013 ◽

2014 ◽

Vol 306 (4) ◽

pp. G346-G356 ◽

Cited By ~ 19

Author(s):

Lenka Polidarová ◽

Lucie Olejníková ◽

Lucia Paušlyová ◽

Martin Sládek ◽

Matúš Soták ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Clock Gene ◽

Clock Genes ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Perinatal Period ◽

Circadian Phase ◽

Clock Gene Expression ◽

The Individual

Colonic morphology and function change significantly during ontogenesis. In mammals, many colonic physiological functions are temporally controlled by the circadian clock in the colon, which is entrained by the central circadian clock in the suprachiasmatic nuclei (SCN). The aim of this present study was to ascertain when and how the circadian clock in the colon develops during the perinatal period and whether maternal cues and/or the developing pup SCN may influence the ontogenesis of the colonic clock. Daily profiles of clock genes Per1, Per2, Cry1, Cry2, Rev-erbα, Bmal1, and Clock expression in the colon underwent significant modifications since embryonic day 20 (E20) through postnatal days (P) 2, 10, 20, and 30 via changes in the mutual phasing among the individual clock gene expression rhythms, their relative phasing to the light-dark regime, and their amplitudes. An adult-like state was achieved around P20. The foster study revealed that during the prenatal period, the maternal circadian phase may partially modulate development of the colonic clock. Postnatally, the absence and/or presence of rhythmic maternal care affected the phasing of the clock gene expression profiles in pups at P10 and P20. A reversal in the colonic clock phase between P10 and P20 occurred in the absence of rhythmic signals from the pup SCN. The data demonstrate ontogenetic maturation of the colonic clock and stress the importance of prenatal and postnatal maternal rhythmic signals for its development. These data may contribute to the understanding of colonic function-related diseases in newborn children.

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Gene Expression Analysis in Cold Stress Conditions Reveals BBX20 and CLO as Potential Biomarkers for Cold Tolerance in Almond

Horticulturae ◽

10.3390/horticulturae7120527 ◽

2021 ◽

Vol 7 (12) ◽

pp. 527

Author(s):

Beatriz Bielsa ◽

Jorge Israel Ávila-Alonso ◽

Ángel Fernández i Martí ◽

Jérôme Grimplet ◽

María José Rubio-Cabetas

Keyword(s):

Gene Expression ◽

Cold Stress ◽

Cold Tolerance ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Limiting Factors ◽

Cold Response ◽

Spring Frost ◽

Phenotype Analysis ◽

Spring Frosts

Late spring frosts can become one of the limiting factors for the expansion of cultivation area towards a harsher climate for the almond [Prunus amygdalus Batsch syn P. dulcis (Mill.) D.A. Webb] crop as spring frost can damage up to 90% of the harvest. In order to identify key genes favoring cold tolerance in almonds, branches from three late-blooming genotypes: ‘Guara’, ‘Soleta’ and ‘Belona’ were exposed at −4 °C during 24 h in a constant climate chamber. Phenotype analysis showed that ‘Guara’ and ‘Soleta’ had a greater acclimation capacity to cold than ‘Belona’. The qRT-PCR BioMark System technology was used to monitor the relative expression of 30 candidate genes with a potential relation to cold response, which are either involved in the ICE-CBF-COR pathway or the independent CBF pathway, and also genes not yet characterized or with unknown function in almond genome. Differences in the gene expression profiles were found among the three studied genotypes and the three time-points of cold exposure (0, 2 and 24 h). BBX20 and CLO genes behaved as differentiator genes between tolerant and susceptible genotypes in cold stress response in almond pistils. In addition, the differences of expression among the tolerant genotypes suggested the intervention of different mechanisms responding to cold stress in almonds.

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Molecular phenotyping using networks, diffusion, and topology: soft tissue sarcoma

Scientific Reports ◽

10.1038/s41598-019-50300-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

James C. Mathews ◽

Maryam Pouryahya ◽

Caroline Moosmüller ◽

Yannis G. Kevrekidis ◽

Joseph O. Deasy ◽

...

Keyword(s):

Gene Expression ◽

Data Analysis ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Suppressor Gene ◽

Wasserstein Distance ◽

The Cancer Genome Atlas ◽

Topological Data Analysis ◽

Tissue Samples ◽

P53 Signaling

Abstract Many biological datasets are high-dimensional yet manifest an underlying order. In this paper, we describe an unsupervised data analysis methodology that operates in the setting of a multivariate dataset and a network which expresses influence between the variables of the given set. The technique involves network geometry employing the Wasserstein distance, global spectral analysis in the form of diffusion maps, and topological data analysis using the Mapper algorithm. The prototypical application is to gene expression profiles obtained from RNA-Seq experiments on a collection of tissue samples, considering only genes whose protein products participate in a known pathway or network of interest. Employing the technique, we discern several coherent states or signatures displayed by the gene expression profiles of the sarcomas in the Cancer Genome Atlas along the TP53 (p53) signaling network. The signatures substantially recover the leiomyosarcoma, dedifferentiated liposarcoma (DDLPS), and synovial sarcoma histological subtype diagnoses, and they also include a new signature defined by activation and inactivation of about a dozen genes, including activation of serine endopeptidase inhibitor SERPINE1 and inactivation of TP53-family tumor suppressor gene TP73.

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Molecular phenotyping using networks, diffusion, and topology: soft tissue sarcoma

10.1101/328054 ◽

2018 ◽

Author(s):

James C Mathews ◽

Maryam Pouryahya ◽

Caroline Moosmüller ◽

Ioannis Kevrekidis ◽

Joseph O Deasy ◽

...

Keyword(s):

Gene Expression ◽

Data Analysis ◽

Kinase Inhibitor ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Suppressor Gene ◽

The Cancer Genome Atlas ◽

Topological Data Analysis ◽

P53 Family ◽

Tissue Samples

AbstractMany biological datasets are high-dimensional yet manifest an underlying order. In this paper, we describe an unsupervised data analysis methodology that operates in the setting of a multivariate dataset and a network which expresses influence between the variables of the given set. The technique involves network geometry employing the Wasserstein distance, global spectral analysis in the form of diffusion maps, and topological data analysis using the Mapper algorithm. The prototypical application is to gene expression profiles obtained from RNA-Seq experiments on a collection of tissue samples, considering only genes whose protein products participate in a known pathway or network of interest. Employing the technique, we discern several coherent states or signatures displayed by the gene expression profiles of the sarcomas in the Cancer Genome Atlas along the p53 signaling network. The signatures substantially recover the leiomyosarcoma, dedifferentiated liposarcoma (DDLPS), and synovial sarcoma histological subtype diagnoses, but they also include a new signature defined by simultaneous activation and inactivation of about a dozen genes, including activation of fibrinolysis inhibitor SERPINE1/PAI and inactivation of p53-family tumor suppressor gene P73 along with cyclin dependent kinase inhibitor 2A CDKN2A/P14ARF.

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Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas

Blood ◽

10.1182/blood-2003-04-1359 ◽

2004 ◽

Vol 103 (5) ◽

pp. 1862-1868 ◽

Cited By ~ 71

Author(s):

Jane Houldsworth ◽

Adam B. Olshen ◽

Giorgio Cattoretti ◽

Gerard B. Donnelly ◽

Julie Teruya-Feldstein ◽

...

Keyword(s):

Gene Expression ◽

B Cell ◽

Expression Profiles ◽

Active Form ◽

Gene Expression Profiles ◽

B Cell Lymphoma ◽

Nuclear Factor Κb ◽

Nuclear Accumulation ◽

The Relationship ◽

Large B Cell

AbstractAlthough it has been suggested that REL is the critical target gene of 2p12-16 amplification in diffuse large B-cell lymphoma (DLBCL), little experimental evidence supports this notion. In the present study, we sought to evaluate the relationship between REL amplification and REL function in a panel of 46 newly diagnosed DLBCLs and to correlate with DLBCL subgroups as identified by gene expression profiles and clinical features. The results indicate that amplification of the REL locus is not associated with accumulation of the active form of REL, as evaluated by immunofluorescence analysis. Upon subgrouping of the DLBCL cases based on gene expression signatures, REL amplification was detected in all subgroups, while high levels of nuclear-located REL were more frequently detected in activated B-cell–like DLBCL. Correlative analyses of REL copy number and REL nuclear accumulation with clinical parameters did not reveal any significant associations. Together these results indicate that 2p12-16 amplification does not lead to abnormal REL activation, suggesting that REL may not be the functional target of the amplification event. Nonetheless, these data indicate that DLBCLs are heterogeneous with respect to REL and thus nuclear factor–κB (NF-κB) activity.

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