Positional cloning of the mouse circadian clock gene.
We used positional cloning to identify the circadian Clock gene in mice. Clock is a large transcription unit with 24 exons spanning approximately 100,000 bp of DNA from which transcript classes of 7.5 and approximately 10 kb arise. Clock encodes a novel member of the bHLH-PAS family of transcription factors. In the Clock mutant allele, an A-->T nucleotide transversion in a splice donor site causes exon skipping and deletion of 51 amino acids in the CLOCK protein. Clock is a unique gene with known circadian function and with features predicting DNA binding, protein dimerization, and activation domains. CLOCK represents the second example of a PAS domain-containing clock protein (besides Drosophila PERIOD), which suggests that this motif may define an evolutionarily conserved feature of the circadian clock mechanism.
King
D P
DP
National Science Foundation Center for Biological Timing, Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
Zhao
Y
Y
Sangoram
A M
AM
Wilsbacher
L D
LD
Tanaka
M
M
Antoch
M P
MP
Steeves
T D
TD
Vitaterna
M H
MH
Kornhauser
J M
JM
Lowrey
P L
PL
Turek
F W
FW
Takahashi
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D056926:CLOCK Proteins; D002642:Chick Embryo; D002874:Chromosome Mapping; D002940:Circadian Rhythm / Q000235:genetics*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D004330:Drosophila / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics*
D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D015534:Trans-Activators; D056926:CLOCK Proteins; C538943:CLOCK protein, human; C538944:Clock protein, mouse