%0 Journal Article %1 Sato2006Feedback %A Sato, Trey K. %A Yamada, Rikuhiro G. %A Ukai, Hideki %A Baggs, Julie E. %A Miraglia, Loren J. %A Kobayashi, Tetsuya J. %A Welsh, David K. %A Kay, Steve A. %A Ueda, Hiroki R. %A Hogenesch, John B. %D 2006 %I Nature Publishing Group %J Nature Genetics %K circadian-clock mammalian %N 3 %P 312--319 %R 10.1038/ng1745 %T Feedback repression is required for mammalian circadian clock function %U http://dx.doi.org/10.1038/ng1745 %V 38 %X Direct evidence for the requirement of transcriptional feedback repression in circadian clock function has been elusive. Here, we developed a molecular genetic screen in mammalian cells to identify mutants of the circadian transcriptional activators CLOCK and BMAL1, which were uncoupled from CRYPTOCHROME (CRY)-mediated transcriptional repression. Notably, mutations in the PER-ARNT-SIM domain of CLOCK and the C terminus of BMAL1 resulted in synergistic insensitivity through reduced physical interactions with CRY. Coexpression of these mutant proteins in cultured fibroblasts caused arrhythmic phenotypes in population and single-cell assays. These data demonstrate that CRY-mediated repression of the CLOCK/BMAL1 complex activity is required for maintenance of circadian rhythmicity and provide formal proof that transcriptional feedback is required for mammalian clock function.

@article{Sato2006Feedback, abstract = {Direct evidence for the requirement of transcriptional feedback repression in circadian clock function has been elusive. Here, we developed a molecular genetic screen in mammalian cells to identify mutants of the circadian transcriptional activators {CLOCK} and {BMAL1}, which were uncoupled from {CRYPTOCHROME} ({CRY})-mediated transcriptional repression. Notably, mutations in the {PER}-{ARNT}-{SIM} domain of {CLOCK} and the C terminus of {BMAL1} resulted in synergistic insensitivity through reduced physical interactions with {CRY}. Coexpression of these mutant proteins in cultured fibroblasts caused arrhythmic phenotypes in population and single-cell assays. These data demonstrate that {CRY}-mediated repression of the {CLOCK}/{BMAL1} complex activity is required for maintenance of circadian rhythmicity and provide formal proof that transcriptional feedback is required for mammalian clock function.}, added-at = {2018-12-02T16:09:07.000+0100}, author = {Sato, Trey K. and Yamada, Rikuhiro G. and Ukai, Hideki and Baggs, Julie E. and Miraglia, Loren J. and Kobayashi, Tetsuya J. and Welsh, David K. and Kay, Steve A. and Ueda, Hiroki R. and Hogenesch, John B.}, biburl = {https://www.bibsonomy.org/bibtex/255bf2b3e4fbc2a9bffff7c4a8b5b4a02/karthikraman}, citeulike-article-id = {520427}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ng1745}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/ng1745}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16474406}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16474406}, day = 12, doi = {10.1038/ng1745}, interhash = {908fe1aa8dbb152ced8ccc9fa85142c1}, intrahash = {55bf2b3e4fbc2a9bffff7c4a8b5b4a02}, issn = {1061-4036}, journal = {Nature Genetics}, keywords = {circadian-clock mammalian}, month = feb, number = 3, pages = {312--319}, pmid = {16474406}, posted-at = {2010-07-19 16:44:21}, priority = {2}, publisher = {Nature Publishing Group}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {Feedback repression is required for mammalian circadian clock function}, url = {http://dx.doi.org/10.1038/ng1745}, volume = 38, year = 2006 }