Publication Date:
2000-05-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shearman, L P -- Sriram, S -- Weaver, D R -- Maywood, E S -- Chaves, I -- Zheng, B -- Kume, K -- Lee, C C -- van der Horst, G T -- Hastings, M H -- Reppert, S M -- HL07901/HL/NHLBI NIH HHS/ -- R01 NS39303/NS/NINDS NIH HHS/ -- R37 HD14427/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2000 May 12;288(5468):1013-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10807566" target="_blank"〉PubMed〈/a〉
Keywords:
ARNTL Transcription Factors
;
Animals
;
Basic Helix-Loop-Helix Transcription Factors
;
Biological Clocks/genetics/*physiology
;
CLOCK Proteins
;
Cell Cycle Proteins
;
Cell Line
;
Cell Nucleus/metabolism
;
Circadian Rhythm/genetics/*physiology
;
Cryptochromes
;
Dimerization
;
*Drosophila Proteins
;
*Eye Proteins
;
Feedback
;
Female
;
Flavoproteins/genetics/*metabolism
;
Gene Expression Regulation
;
In Situ Hybridization
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Models, Biological
;
Mutation
;
Nuclear Proteins/genetics/*metabolism
;
Period Circadian Proteins
;
*Photoreceptor Cells, Invertebrate
;
Protein Biosynthesis
;
RNA/metabolism
;
Receptors, G-Protein-Coupled
;
Suprachiasmatic Nucleus/*metabolism
;
Trans-Activators/genetics/metabolism
;
Transcription Factors/genetics/*metabolism
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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