Cryptochrome 1 regulates the circadian clock through dynamic interactions with the BMAL1 C terminus
| العنوان: | Cryptochrome 1 regulates the circadian clock through dynamic interactions with the BMAL1 C terminus |
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| المؤلفون: | Chelsea Gustafson, Hsiau-Wei Lee, Carrie L. Partch, Andrew C. Liu, Patrick J. Sammons, Nicole C. Parsley, Sanjoy K. Khan, Chidambaram Ramanathan, Haiyan Xu |
| المصدر: | Nature Structural & Molecular Biology. 22:476-484 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Mice, Knockout, Genetics, endocrine system, Period (gene), Circadian clock, ARNTL Transcription Factors, Repressor, Fibroblasts, Biology, Cell biology, Cryptochromes, Mice, Cryptochrome, Structural Biology, Circadian Clocks, Animals, Humans, Circadian rhythm, Molecular Biology, Psychological repression, Transcription factor, Cells, Cultured, Cryptochrome-1 |
| الوصف: | The molecular circadian clock in mammals is generated from transcriptional activation by the bHLH-PAS transcription factor CLOCK-BMAL1 and subsequent repression by PERIOD and CRYPTOCHROME (CRY). The mechanism by which CRYs repress CLOCK-BMAL1 to close the negative feedback loop and generate 24-h timing is not known. Here we show that, in mouse fibroblasts, CRY1 competes for binding with coactivators to the intrinsically unstructured C-terminal transactivation domain (TAD) of BMAL1 to establish a functional switch between activation and repression of CLOCK-BMAL1. TAD mutations that alter affinities for co-regulators affect the balance of repression and activation to consequently change the intrinsic circadian period or eliminate cycling altogether. Our results suggest that CRY1 fulfills its role as an essential circadian repressor by sequestering the TAD from coactivators, and they highlight regulation of the BMAL1 TAD as a critical mechanism for establishing circadian timing. |
| تدمد: | 1545-9985 1545-9993 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e3719a4d1b8b4818069872567379a16 https://doi.org/10.1038/nsmb.3018 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8e3719a4d1b8b4818069872567379a16 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15459985 15459993 |
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