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Accueil > Agenda > Les séminaires Jean Roche > Les horloges circadiennes périphériques des mammifères.

Les horloges circadiennes périphériques des mammifères.

Lundi 20 2006,11h, salle Lissitzky.

Bibliographie

1 : <span title="Journal of molecular medicine (Berlin, Germany)"><a href="javascript:AL_get(this, 'jour', 'J Mol Med.');">J Mol Med. 2005 Sep ;83(9):693-9. Epub 2005 Aug 12.


<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3055&uid=16096739&db=pubmed&url=http://dx.doi.org/10.1007/s00109-005-0697-6" target="_blank">Click here to read 
Comment in :
  • <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16096738&itool=pubmed_Abstract">J Mol Med. 2005 Sep ;83(9):655-6.


Atypical patterns of circadian clock gene expression in human peripheral blood mononuclear cells.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Teboul+M%22%5BAuthor%5D" title="Click to search for citations by this author.">Teboul M, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Barrat%2DPetit+MA%22%5BAuthor%5D" title="Click to search for citations by this author.">Barrat-Petit MA, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Li+XM%22%5BAuthor%5D" title="Click to search for citations by this author.">Li XM, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Claustrat+B%22%5BAuthor%5D" title="Click to search for citations by this author.">Claustrat B, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Formento+JL%22%5BAuthor%5D" title="Click to search for citations by this author.">Formento JL, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Levi+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Levi F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Milano+G%22%5BAuthor%5D" title="Click to search for citations by this author.">Milano G.

Universite de Nice-Sophia Antipolis, CNRS FRE 2721, Parc Valrose, 06108 Nice Cedex 2, France. teboulm unice.fr

Circadian ( approximately 24 h) rhythms in physiology and behaviour are observed in all mammals, including humans. These rhythms are generated by circadian clocks located in the hypothalamus and also in most peripheral tissues. Clock genes are essential components of circadian clocks, and mutations or polymorphisms within several of them have been associated with circadian disorders in humans. However, information about human clock gene expression has remained very limited. Peripheral blood mononuclear cells (PBMCs) represent an ideal material to investigate non-invasively the human clock at the molecular level. In the present study, we analysed the expression of three key clock genes, PER2, BMAL1 and REV-ERBalpha in PBMCs from ten healthy humans over a 24-h cycle. PER2 and BMAL1 were found to oscillate throughout the light-dark cycle in all subjects. Interestingly, despite normal melatonin and cortisol secretion patterns, two groups of subjects could be distinguished with significantly different mean PER2 and BMAL1 acrophases. BMAL1 oscillated with approximately the same phase as PER2, instead of being anti-phasic as anticipated from data previously obtained in other peripheral tissues. Furthermore, this unusual phase relationship of PER2 and BMAL1 in human PBMCs was associated with a constant expression of REV-ERBalpha, a crucial regulator of BMAL1, which is highly rhythmic in many other systems. These results reveal the existence of different chronotypes of clock gene expression patterns and suggest specific regulatory mechanisms in human PBMCs.


2 : <span title="Pathologie-biologie."><a href="javascript:AL_get(this, 'jour', 'Pathol Biol (Paris).');">Pathol Biol (Paris). 2005 Jun ;53(5):295-9. Epub 2005 Jan 20.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3048&uid=15939142&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0369-8114%2804%2900300-1" target="_blank">Click here to read 
[Algorithm of determination of circadian gene expression profiles analysed with DNA microarrays]

[Article in French]

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Beau+J%22%5BAuthor%5D" title="Click to search for citations by this author.">Beau J, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Lacoche+S%22%5BAuthor%5D" title="Click to search for citations by this author.">Lacoche S, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Grechez%2DCassiau+A%22%5BAuthor%5D" title="Click to search for citations by this author.">Grechez-Cassiau A, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Levi+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Levi F.

Chronotherapeutique des cancers, Inserm E 0354, hopital Paul-Brousse, 12, avenue P. Vaillant-Couturier, 94800 Villejuif, France. <a class="moz-txt-link-abbreviated" href="/agenda/les-seminaires-jean-roche/les-horloges-circadiennes#" title="beau..åt..vjf.inserm.fr" onclick="location.href=lancerlien('beau,5adab4173f6a0,vjf.inserm.fr',',5adab4173f6a0,'); return false;">beau vjf.inserm.fr

DNA microarrays allow to simultaneously determine the expression level of thousands of genes. A nycthemeral study must enable to conclude which ones show a circadian rhythm. Two aspects prove this to be quite difficult : firstly, what does "circadian" exactly mean and how to quantify this qualification, and secondly which genes pertain to this definition. Our method, derived from linear optimisation procedures, consists in determining a cost function, depending from magnitudes characterising the notion of circadian rhythm. Given number of genes present on the microarray are known to be expressed rhythmically ; their time series are considered as reference series. We have further constructed random series having the same temporal structure as the circadian gene series. We then carried out an optimisation procedure to determine the weighting coefficients in order to obtain a cost function value which orders the time series as follows : the reference series are in the first rows and the random series have low scores. We have tested this method on over 6000 genes expressed in mouse liver. We obtained a circadian gene detection probability of 100% with a false positive rate inferior to 1%.


3 : <span title="Journal of molecular endocrinology."><a href="javascript:AL_get(this, 'jour', 'J Mol Endocrinol.');">J Mol Endocrinol. 2004 Dec ;33(3):585-608.

<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3051&uid=15591021&db=pubmed&url=http://jme.endocrinology-journals.org/cgi/pmidlookup?view=long&pmid=15591021" target="_blank">Click here to read 
The orphan receptor Rev-erbalpha gene is a target of the circadian clock pacemaker.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Triqueneaux+G%22%5BAuthor%5D" title="Click to search for citations by this author.">Triqueneaux G, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Thenot+S%22%5BAuthor%5D" title="Click to search for citations by this author.">Thenot S, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Kakizawa+T%22%5BAuthor%5D" title="Click to search for citations by this author.">Kakizawa T, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Antoch+MP%22%5BAuthor%5D" title="Click to search for citations by this author.">Antoch MP, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Safi+R%22%5BAuthor%5D" title="Click to search for citations by this author.">Safi R, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Takahashi+JS%22%5BAuthor%5D" title="Click to search for citations by this author.">Takahashi JS, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Laudet+V%22%5BAuthor%5D" title="Click to search for citations by this author.">Laudet V.

Laboratoire de Biologie Moleculaire et Cellulaire, CNRS UMR 5161, Ecole Normale Superieur de Lyon, 46 allee d’Italie, 69364 Lyon cedex, France.

Rev-erbalpha is a ubiquitously expressed orphan nuclear receptor which functions as a constitutive transcriptional repressor and is expressed in vertebrates according to a robust circadian rhythm. We report here that two Rev-erbalpha mRNA isoforms, namely Rev-erbalpha1 and Rev-erbalpha 2, are generated through alternative promoter usage and that both show a circadian expression pattern in an in vitro system using serum-shocked fibroblasts. Both promoter regions P1 (Rev-erbalpha1) and P2 (Rev-erbalpha2) contain several E-box DNA sequences which function as response elements for the core circadian-clock components : CLOCK and BMAL1. The CLOCK-BMAL1 heterodimer stimulates the activity of both P1 and P2 promoters in transient transfection assay by 3-6-fold. This activation was inhibited by the overexpression of CRY1, a component of the negative limb of the circadian transcriptional loop. Critical E-box elements were mapped within both promoters. This regulation is conserved in vertebrates since we found that the CLOCK-BMAL1 heterodimer also regulates the zebrafish Rev-erbalpha gene. In line with these data Rev-erbalpha circadian expression was strongly impaired in the livers of Clock mutant mice and in the pineal glands of zebrafish embryos treated with Clock and Bmal1 antisense oligonucleotides. Together these data demonstrate that CLOCK is a critical regulator of Rev-erbalpha circadian gene expression in evolutionarily distant vertebrates and suggest a role for Rev-erbalpha in the circadian clock output.


4 : <span title="Cancer research."><a href="javascript:AL_get(this, 'jour', 'Cancer Res.');">Cancer Res. 2004 Nov 1 ;64(21):7879-85.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3051&uid=15520194&db=pubmed&url=http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15520194" target="_blank">Click here to read 
Effects of chronic jet lag on tumor progression in mice.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Filipski+E%22%5BAuthor%5D" title="Click to search for citations by this author.">Filipski E, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22King+VM%22%5BAuthor%5D" title="Click to search for citations by this author.">King VM, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Wu+MW%22%5BAuthor%5D" title="Click to search for citations by this author.">Wu MW, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Claustrat+B%22%5BAuthor%5D" title="Click to search for citations by this author.">Claustrat B, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Grechez%2DCassiau+A%22%5BAuthor%5D" title="Click to search for citations by this author.">Grechez-Cassiau A, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Guettier+C%22%5BAuthor%5D" title="Click to search for citations by this author.">Guettier C, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Hastings+MH%22%5BAuthor%5D" title="Click to search for citations by this author.">Hastings MH, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Francis+L%22%5BAuthor%5D" title="Click to search for citations by this author.">Francis L.

INSERM E 0354 Cancer chronotherapeutics, Hopital Paul Brousse, Villejuif Cedex, France.

Frequent transmeridian flights or predominant work at night can increase cancer risk. Altered circadian rhythms also predict for poor survival in cancer patients, whereas physical destruction of the suprachiasmatic nuclei (SCN), the hypothalamic circadian pacemaker, accelerates tumor growth in mice. Here we tested the effect of functional disruption of circadian system on tumor progression in a novel experimental model of chronic jet lag. B6D2F(1) mice were synchronized with 12 hours of light and 12 hours of darkness or underwent repeat 8-hour advances of the light/dark cycle every 2 days before inoculation of Glasgow osteosarcoma. The 24-hour changes were assessed for plasma corticosterone, clock protein mPER1 expression in the SCN, and mRNA expression of clock genes mPer2 and mRev-erbalpha in liver and tumor. Time series were analyzed by spectral analysis and/or Cosinor. Differences were compared with analysis of variance (ANOVA). The 24-hour rest/activity cycle was ablated, and the rhythms of body temperature, serum corticosterone, and mPER1 protein expression in the SCN were markedly altered in jet-lagged mice as compared with controls (ANOVA, P < 0.001 for corticosterone and P = 0.01 for mPER1). Tumor grew faster in the jet-lagged animals as compared with controls (ANOVA, P < 0.001), whereas exposure to constant light or darkness had no effect (ANOVA, P = 0.66 and P = 0.8, respectively). The expression of mPer2 and mRev-erbalpha mRNAs in controls showed significant circadian rhythms in the liver (P = 0.006 and P = 0.003, respectively, Cosinor) and in the tumor (P = 0.04 and P < 0.001). Both rhythms were suppressed in the liver (P = 0.2 and P = 0.1, respectively, Cosinor) and in the tumor (P = 0.5) of jet-lagged mice. Altered environmental conditions can disrupt circadian clock molecular coordination in peripheral organs including tumors and play a significant role in malignant progression.


5 : <span title="Medecine sciences : M/S."><a href="javascript:AL_get(this, 'jour', 'Med Sci (Paris).');">Med Sci (Paris). 2004 Jun-Jul ;20(6-7):628-9.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=4587&uid=15329807&db=pubmed&url=http://www.erudit.org/revue/ms/2004/v20/n6-7/008676ar.html" target="_blank">Click here to read 
[No hierarchy in mammalian circadian system]

[Article in French]

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Teboul+M%22%5BAuthor%5D" title="Click to search for citations by this author.">Teboul M, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F.


6 : <span title="Journal of molecular endocrinology."><a href="javascript:AL_get(this, 'jour', 'J Mol Endocrinol.');">J Mol Endocrinol. 2004 Aug ;33(1):87-97.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3051&uid=15291745&db=pubmed&url=http://jme.endocrinology-journals.org/cgi/pmidlookup?view=long&pmid=15291745" target="_blank">Click here to read 
Expression of the orphan nuclear receptor ERRalpha is under circadian regulation in estrogen-responsive tissues.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Horard+B%22%5BAuthor%5D" title="Click to search for citations by this author.">Horard B, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Rayet+B%22%5BAuthor%5D" title="Click to search for citations by this author.">Rayet B, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Triqueneaux+G%22%5BAuthor%5D" title="Click to search for citations by this author.">Triqueneaux G, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Laudet+V%22%5BAuthor%5D" title="Click to search for citations by this author.">Laudet V, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Vanacker+JM%22%5BAuthor%5D" title="Click to search for citations by this author.">Vanacker JM.

Laboratoire de Biologie Moleculaire de la Cellule, CNRS UMR 5161, IFR128 Biosciences Lyon-Gerland, Ecole Normale Superieure de Lyon, 46 allee d’Italie, 69007 Lyon, France.

Circadian gene expression has been demonstrated in many tissues and involves both positive and negative regulatory loops. The potential interferences of circadian rhythmicity with other well-known biologic rhythms, such as the ovarian cycle, at least in part controlled by estrogens, has not been questioned. The estrogen receptor-related receptor (ERR)alpha is an orphan nuclear receptor that is widely expressed in estrogen-responsive tissues such as liver, uterus and bone. In addition, expression of the ERRalpha gene has been proposed to be transcriptionally controlled by estrogens in the uterus. Here we show that the expression of ERRalpha displays a circadian rhythmicity in liver, bone and uterus. This is in contrast to other uterine estrogen-regulated genes. Analysis of clock/clock mutant mice shows that ERRalpha is an output gene of the circadian clock oscillator. The expression of clock-control genes, such as Bmal1 and Rev-erbalpha, also displays diurnal oscillations in the uterus, but not in bone. In this tissue, however, Per2 displayed a rhythmic expression, altogether suggesting unconventional loops in the regulation of circadian rhythm in bone.


7 : <span title="Medecine sciences : M/S."><a href="javascript:AL_get(this, 'jour', 'Med Sci (Paris).');">Med Sci (Paris). 2004 Feb ;20(2):146-7.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=4587&uid=14997431&db=pubmed&url=http://www.erudit.org/revue/ms/2004/v20/n2/007670ar.html" target="_blank">Click here to read 
[Liver regeneration and the clock]

[Article in French]

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Teboul+M%22%5BAuthor%5D" title="Click to search for citations by this author.">Teboul M, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Rayet+B%22%5BAuthor%5D" title="Click to search for citations by this author.">Rayet B, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F.


8 : <span title="The Journal of biological chemistry."><a href="javascript:AL_get(this, 'jour', 'J Biol Chem.');">J Biol Chem. 2004 Jan 9 ;279(2):1141-50. Epub 2003 Oct 27
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3051&uid=14581485&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=14581485" target="_blank">Click here to read 
The transcriptional repressor STRA13 regulates a subset of peripheral circadian outputs.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Grechez%2DCassiau+A%22%5BAuthor%5D" title="Click to search for citations by this author.">Grechez-Cassiau A, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Panda+S%22%5BAuthor%5D" title="Click to search for citations by this author.">Panda S, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Lacoche+S%22%5BAuthor%5D" title="Click to search for citations by this author.">Lacoche S, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Teboul+M%22%5BAuthor%5D" title="Click to search for citations by this author.">Teboul M, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Azmi+S%22%5BAuthor%5D" title="Click to search for citations by this author.">Azmi S, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Laudet+V%22%5BAuthor%5D" title="Click to search for citations by this author.">Laudet V, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Hogenesch+JB%22%5BAuthor%5D" title="Click to search for citations by this author.">Hogenesch JB, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Taneja+R%22%5BAuthor%5D" title="Click to search for citations by this author.">Taneja R, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F.

Universite de Nice-Sophia Antipolis, CNRS UMR 6078, La Darse, 06230 Villefranche/mer, France.

Central and peripheral mammalian circadian clocks regulate a variety of behavioral and physiological processes through the rhythmic transcription of hundreds of clock-controlled genes. The circadian expression of many transcriptional regulators suggests that a major part of this circadian gene network is indirectly regulated by clock genes. Here we show that the basic helix-loop-helix transcriptional repressor Stra13 is rhythmically expressed in mouse peripheral organs. The circadian transcription of Stra13 is mediated by a response element recognized by the CLOCK-BMAL1 heterodimer and located in the proximal promoter region. CLOCK-BMAL1-dependent activation of Stra13 is strongly repressed by CRY1 and also by STRA13 itself. To determine putative Stra13 output genes, we performed microarray analyses of differential gene expression in the liver between wild type and Stra13-/- mice and identified 42 target genes including a subset of 20 previously known as clock-controlled genes. Importantly, we demonstrate that circadian gene expression of the serum protein insulin-like growth factor-binding protein 1 and of the NKG2D receptor ligand retinoic acid early transcript was suppressed in Stra13-/- mice. These biochemical and genetic data establish a role for the basic helix-loop-helix repressor STRA13 as a circadian output regulator in the periphery.


9 : <span title="Pathologie-biologie."><a href="javascript:AL_get(this, 'jour', 'Pathol Biol (Paris).');">Pathol Biol (Paris). 2003 Jun ;51(4):208-9.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3048&uid=12852991&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0369811403000312" target="_blank">Click here to read 
[Global analysis of circadian gene expression]

[Article in French]

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Lacoche+S%22%5BAuthor%5D" title="Click to search for citations by this author.">Lacoche S, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F.

Universite de Nice-Sophia-Antipolis, CNRS UMR 6078, 284 chemin du Lazaret, 06230, Villefranche-sur-mer, France.

A major goal of chronobiology is to identify clock-controlled genes. The expression of thousands of genes can be monitored simultaneously using DNA microarrays. Application of DNA microarray technology to the field of circadian rhythm has already shown that a number of genes coding for proteins involved in very diverse functions are under the control of the circadian clock.


10 : <span title="Medecine sciences : M/S."><a href="javascript:AL_get(this, 'jour', 'Med Sci (Paris).');">Med Sci (Paris). 2003 Apr ;19(4):411-3.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=4587&uid=12836212&db=pubmed&url=http://www.erudit.org/revue/ms/2003/v19/n4/006490ar.html" target="_blank">Click here to read 
[The orphan nuclear receptor Rev-erb alpha is a major component of the circadian clock]

[Article in French]

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Teboul+M%22%5BAuthor%5D" title="Click to search for citations by this author.">Teboul M, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F.


11 : <span title="Gene expression patterns : GEP."><a href="javascript:AL_get(this, 'jour', 'Gene Expr Patterns.');">Gene Expr Patterns. 2003 Jun ;3(3):319-24.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3048&uid=12799078&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S1567133X03000504" target="_blank">Click here to read 
Differential regulation of Period 2 and Period 3 expression during development of the zebrafish circadian clock.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Thisse+C%22%5BAuthor%5D" title="Click to search for citations by this author.">Thisse C, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Thisse+B%22%5BAuthor%5D" title="Click to search for citations by this author.">Thisse B, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Laudet+V%22%5BAuthor%5D" title="Click to search for citations by this author.">Laudet V.

Universite de Nice-Sophia Antipolis, CNRS UMR 6078, 284 chemin du Lazaret, 06230 cedex, Villefranche/mer, France.

Circadian ( approximately 24h) clocks are endogenous time-keeping systems that drive the daily biological rhythms observed in most living organisms. The oscillation is generated by a transcriptional/translational autoregulatory feedback loop that is reset by external time cues such as the light/dark cycle and which in turn controls rhythms in physiology and behavior through downstream clock-controlled genes (Nature 417 (2002) 329). Genetic and biochemical analysis of Drosophila and mammalian clock genes has provided a comprehensive model for the molecular oscillator that generates these rhythms, but the ontogeny of this oscillator remains poorly understood. A circadian oscillator involving the clock genes Per3 and Rev-erb alpha was identified during early development in zebrafish (Science 289 (2000) 297). Here, we report the isolation of zebrafish Per2 and show the presence of a Per2 maternal mRNA in early embryos as for Per3. However, Per2 rhythmic expression occurs late during embryogenesis as compared to that of Per3. Furthermore, our data indicate that Per2 is not required during embryogenesis for the rhythmicity of physiological outputs such as melatonin synthesis. In addition, Per2 but not Per3 is constitutively expressed in the developing olfactory bulb and pituitary. This differential spatio-temporal expression patterns suggest specific roles for Per2 and Per3 in the establishment of the embryonic circadian system.


12 : <span title="Journal of molecular endocrinology."><a href="javascript:AL_get(this, 'jour', 'J Mol Endocrinol.');">J Mol Endocrinol. 2003 Apr ;30(2):197-211.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3051&uid=12683943&db=pubmed&url=http://jme.endocrinology-journals.org/cgi/pmidlookup?view=long&pmid=12683943" target="_blank">Click here to read 
A specific and unusual nuclear localization signal in the DNA binding domain of the Rev-erb orphan receptors.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Chopin%2DDelannoy+S%22%5BAuthor%5D" title="Click to search for citations by this author.">Chopin-Delannoy S, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Thenot+S%22%5BAuthor%5D" title="Click to search for citations by this author.">Thenot S, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Buisine+E%22%5BAuthor%5D" title="Click to search for citations by this author.">Buisine E, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Begue+A%22%5BAuthor%5D" title="Click to search for citations by this author.">Begue A, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Duterque%2DCoquillaud+M%22%5BAuthor%5D" title="Click to search for citations by this author.">Duterque-Coquillaud M, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Laudet+V%22%5BAuthor%5D" title="Click to search for citations by this author.">Laudet V.

Institut de Biologie de Lille, CNRS UMR 8526, Institut Pasteur de Lille, 1 rue Calmette, 59021 Lille cedex, France.

The orphan receptors Rev-erbalpha and Rev-erbbeta are members of the nuclear receptors superfamily and act as transcriptional repressors. Rev-erbalpha is expressed with a robust circadian rhythm and is involved in liver metabolism through repression of the ApoA1 gene, but no role has been yet defined for Rev-erbbeta. To gain better understanding of their function and mode of action, we characterized the proteins encoded by these two genes. Both Rev-erbalpha and Rev-erbbeta proteins were nuclear when transiently transfected in COS-1 cells. The major nuclear location signal (NLS) of Rev-erbalpha is in the amino-terminal region of the protein. Fusion of green fluorescent protein (GFP) to the amino terminus of Rev-erbalpha deletion mutants showed that the NLS is located within a 53 amino acid segment of the DNA binding domain (DBD). The homologous region of Rev-erbbeta fused to GFP also targeted the fusion protein to the nucleus, suggesting that the location of this NLS is conserved among all the Rev-erb group members. Interestingly, members of the phylogenetically closest nuclear orphan receptor group (ROR), which exhibit 58% amino acid identity with Rev-erb in the DBD, do not have their NLS located within the DBD. GFP/DBD. RORalpha or GFP/DBD.RORbeta remained cytoplasmic, in contrast to GFP/DBD. Rev-erb fusion proteins. Alignment of human Rev-erb and ROR DBD amino acid sequences predicted that the two basic residues, K167 and R168, located just upstream from the second zinc finger, could play a critical part in the nuclear localization of Rev-erb proteins. Substitution of these two residues with those found in ROR, in the GFP/DBD. Rev-erb context, resulted in cytoplasmic proteins. In contrast, the reverse mutation of the GFP/DBD. RORalpha towards the Rev-erbalpha residues targeted the fusion protein to the nucleus. Our data demonstrate that Rev-erb proteins contain a functional NLS in the DBD. Its location is unusual within the nuclear receptor superfamily and suggests that Rev-erb orphan receptors control their intracellular localization via a mechanism different from that of other nuclear receptors.


13 : <span title="Trends in genetics : TIG."><a href="javascript:AL_get(this, 'jour', 'Trends Genet.');">Trends Genet. 2002 Dec ;18(12):595-7.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3048&uid=12446134&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0168952502027944" target="_blank">Click here to read 
Circadian clock and microarrays : mammalian genome gets rhythm.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Laudet+V%22%5BAuthor%5D" title="Click to search for citations by this author.">Laudet V.


14 : <span title="The Journal of biological chemistry."><a href="javascript:AL_get(this, 'jour', 'J Biol Chem.');">J Biol Chem. 2001 Dec 14 ;276(50):46751-8. Epub 2001 Oct 11.
<a href="http://www.ncbi.nlm.nih.gov/entrez/utils/lofref.fcgi?PrId=3051&uid=11598123&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=11598123" target="_blank">Click here to read 
Circadian regulation of diverse gene products revealed by mRNA expression profiling of synchronized fibroblasts.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Grundschober+C%22%5BAuthor%5D" title="Click to search for citations by this author.">Grundschober C, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Delaunay+F%22%5BAuthor%5D" title="Click to search for citations by this author.">Delaunay F, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Puhlhofer+A%22%5BAuthor%5D" title="Click to search for citations by this author.">Puhlhofer A, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Triqueneaux+G%22%5BAuthor%5D" title="Click to search for citations by this author.">Triqueneaux G, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Laudet+V%22%5BAuthor%5D" title="Click to search for citations by this author.">Laudet V, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Bartfai+T%22%5BAuthor%5D" title="Click to search for citations by this author.">Bartfai T, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Nef+P%22%5BAuthor%5D" title="Click to search for citations by this author.">Nef P.

Central Nervous System Department, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland.

Genes under a 24-h regulation period may represent drug targets relevant to diseases involving circadian dysfunctions. As a testing model of the circadian clock system, we have used synchronized rat fibroblasts that are known to express at least six genes in a circadian fashion. We have determined the expression patterns of 9957 transcripts every 4 h over a total period of 76 h using high density oligonucleotide microarrays. The spectral analysis of our mRNA profiling data indicated that approximately 2% (85 genes) of all expressed genes followed a robust circadian pattern. We have confirmed the circadian expression of previously known clock or clock-driven genes, and we identified 81 novel circadian genes. The majority of the circadian-regulated gene products are known and are involved in diverse cellular functions. We have classified these circadian genes in seven clusters according to their phase of cycling. Our pathway analysis of the mRNA profiling data strongly suggests a direct link between circadian rhythm and cell cycle.

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