The BMAL1 C terminus regulates the circadian transcription feedback loop
العنوان: | The BMAL1 C terminus regulates the circadian transcription feedback loop |
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المؤلفون: | Filippo Tamanini, Maya Yasuda, Takao Kondo, Kazuhiro Yagita, Iori Yamanaka, Akira Morita, Yota B. Kiyohara, Hiroki R. Ueda, Yukiko Sugisawa, Sayaka Tagao, Gijsbertus T. J. van der Horst |
المساهمون: | Molecular Genetics, Cell biology |
المصدر: | Proceedings of the National Academy of Sciences of the U.S.A., 103(26), 10074-10079. National Academy of Sciences |
بيانات النشر: | National Academy of Sciences, 2006. |
سنة النشر: | 2006 |
مصطلحات موضوعية: | Transcriptional Activation, endocrine system, Transcription, Genetic, Circadian clock, CLOCK Proteins, E-box, Biology, RAR-related orphan receptor alpha, Mice, Cryptochrome, Basic Helix-Loop-Helix Transcription Factors, Animals, Circadian rhythm, Cells, Cultured, Sequence Deletion, Feedback, Physiological, Genetics, Multidisciplinary, Flavoproteins, ARNTL Transcription Factors, Fibroblasts, Biological Sciences, Circadian Rhythm, Rats, Cryptochromes, Repressor Proteins, Gene Expression Regulation, Trans-Activators, Biological Assay, Cryptochrome-1 |
الوصف: | The circadian clock is driven by cell-autonomous transcription/translation feedback loops. The BMAL1 transcription factor is an indispensable component of the positive arm of this molecular oscillator in mammals. Here, we present a molecular genetic screening assay for mutant circadian clock proteins that is based on real-time circadian rhythm monitoring in cultured fibroblasts. By using this assay, we identified a domain in the extreme C terminus of BMAL1 that plays an essential role in the rhythmic control of E-box-mediated circadian transcription. Remarkably, the last 43 aa of BMAL1 are required for transcriptional activation, as well as for association with the circadian transcriptional repressor CRYPTOCHROME 1 (CRY1), depending on the coexistence of CLOCK protein. C-terminally truncated BMAL1 mutant proteins still associate with mPER2 (another protein of the negative feedback loop), suggesting that an additional repression mechanism may converge on the N terminus. Taken together, these results suggest that the C-terminal region of BMAL1 is involved in determining the balance between circadian transcriptional activation and suppression. |
تدمد: | 1091-6490 0027-8424 |
DOI: | 10.1073/pnas.0601416103 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b959a16810f7e9100232c2243d8f1df4 https://doi.org/10.1073/pnas.0601416103 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....b959a16810f7e9100232c2243d8f1df4 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 10916490 00278424 |
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DOI: | 10.1073/pnas.0601416103 |