Interacting Molecular Loops in the Mammalian Circadian Clock

• Lauren P. Shearman

  Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.

• Sathyanarayanan Sriram

  Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.

• David R. Weaver

  Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.

• Elizabeth S. Maywood

  Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

• Inẽs Chaves

  Medical Genetic Center, Department of Cell Biology and Genetics, Erasmus University, 3000 DR Rotterdam, Netherlands.

• Binhai Zheng

  Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

• Kazuhiko Kume

  Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.

• Cheng Chi Lee

  Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

• Gijsbertus T. J. van der

• Horst

  Medical Genetic Center, Department of Cell Biology and Genetics, Erasmus University, 3000 DR Rotterdam, Netherlands.

• Michael H. Hastings

  Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

• Steven M. Reppert

  Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.

抄録

We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback loops. Analysis of Clock/Clock mutant mice, homozygous Period2 Brdm1 mutants, and Cryptochrome -deficient mice reveals substantially altered Bmal1 rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal1 loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the Bmal1 loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles.

収録刊行物

• Science

  Science 288 (5468), 1013-1019, 2000-05-12

  American Association for the Advancement of Science (AAAS)

キーワード

• Multidisciplinary

詳細情報

• CRID: 1361699994325537536
• NII論文ID: 80012257514
• DOI: 10.1126/science.288.5468.1013
• ISSN: 10959203
• ISSN: 00368075
• Web Site: https://www.science.org/doi/pdf/10.1126/science.288.5468.1013
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