Expression levels of estrogen receptor β are modulated by components of the molecular clock
Autor: | Juliette Rambaud, Ingemar Pongratz, Ingrid Masse, Jan-Ake Gustafsson, Wen Cai, Michèle Teboul, Vincent Laudet, Franck Delaunay, Gérard Benoit |
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Přispěvatelé: | Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon) |
Jazyk: | angličtina |
Rok vydání: | 2008 |
Předmět: |
medicine.medical_specialty
Transcription Genetic [SDV]Life Sciences [q-bio] Circadian clock Molecular Sequence Data Estrogen receptor CLOCK Proteins Sequence Homology Cell Cycle Proteins Biology RAR-related orphan receptor alpha Cell Line 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Basic Helix-Loop-Helix Transcription Factors Animals Estrogen Receptor beta Humans [INFO]Computer Science [cs] Circadian rhythm RNA Messenger RNA Small Interfering Molecular Biology Lung Estrogen receptor beta 030304 developmental biology Mice Knockout 0303 health sciences ARNTL Transcription Factors Base Sequence Cell Biology Articles Period Circadian Proteins Circadian Rhythm ESTROGEN Endocrinology Gene Expression Regulation Trans-Activators Sequence Alignment 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Molecular and Cellular Biology Molecular and Cellular Biology, American Society for Microbiology, 2008, 28 (2), pp.784-793. ⟨10.1128/MCB.00233-07⟩ Molecular and Cellular Biology, 2008, 28 (2), pp.784-793. ⟨10.1128/MCB.00233-07⟩ |
ISSN: | 0270-7306 1098-5549 |
DOI: | 10.1128/MCB.00233-07⟩ |
Popis: | International audience; Circadian regulation of gene expression plays a major role in health and disease. The precise role of the circadian system remains to be clarified, but it. is known that circadian proteins generate physiological rhythms in organisms by regulating clock-controlled target genes. The estrogen receptor beta (ER beta) is, together with ER alpha, a member of the nuclear receptor superfamily and a key mediator of estrogen action. Interestingly, recent studies show that disturbed circadian rhythmicity in humans can increase the risk of reproductive malfunctions, suggesting a link between the circadian system and ER-mediated transcription pathways. Here, we identify a novel level of regulation of estrogen signaling where ER beta, but not ER alpha, is controlled by circadian clock proteins. We show that ER beta mRNA levels fluctuate in different peripheral tissues following a robust circadian pattern, with a peak at the light-dark transition, which is maintained under free-running conditions. Interestingly, this oscillation is abolished in clock-deficient BMAL1 knockout mice. Circadian control of ER beta expression is exerted through a conserved E-box element in the ER beta promoter region that recruits circadian regulatory factors. Furthermore, using small interfering RNA-mediated knockdown assays, we show that the expression levels of the circadian regulatory factors directly influence estrogen signaling by regulating the intracellular levels of endogenous ER beta. |
Databáze: | OpenAIRE |
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