PMID- 10198158
OWN - NLM
STAT- MEDLINE
DCOM- 19990506
LR  - 20091119
IS  - 0888-7543 (Print)
IS  - 0888-7543 (Linking)
VI  - 57
IP  - 2
DP  - 1999 Apr 15
TI  - Molecular cloning and characterization of the human CLOCK gene: expression in the
      suprachiasmatic nuclei.
PG  - 189-200
AB  - The Clock gene is an essential regulator of circadian rhythms. It encodes a
      member of the basic helix-loop-helix/PER-ARNT-SIM family of transcription factors
      known to play a central role in the control of diverse cellular events.
      Previously we described the functional identification and molecular isolation of 
      the Clock gene in the mouse, its interaction with the BMAL1 protein, and the role
      of this complex as a transcriptional activator in the circadian pacemaker. Here, 
      we report the cloning, exon organization, chromosomal location, and mRNA
      expression of the human CLOCK gene. The coding sequence of human CLOCK extends
      for 2538 bp and is 89% identical to its mouse ortholog; its deduced amino acid
      sequence is 846 residues long and is 96% identical to mouse CLOCK. Radiation
      hybrid mapping localized human CLOCK to the long arm of human chromosome 4
      (4q12). Direct sequencing of a genomic CLOCK clone indicated that the coding
      sequence of human CLOCK extends over 20 exons and that its intron/exon
      organization is identical to that of the mouse ortholog. Northern blot analysis
      indicated widespread expression of two major transcripts of 8 and 10 kb, and in
      situ hybridization of human brain tissue revealed elevated expression of CLOCK
      mRNA in the suprachiasmatic nuclei, the locus of circadian control in mammals,
      and in the cerebellum. Comparison of cDNA clones revealed two single nucleotide
      polymorphisms in noncoding sequence flanking the CLOCK open reading frame. The
      central role of Clock in the organization of circadian rhythms suggests that it
      will be a useful candidate gene for genetic analyses of disorders associated with
      dysfunction of the circadian system.
CI  - Copyright 1999 Academic Press.
FAU - Steeves, T D
AU  - Steeves TD
AD  - Department of Neurobiology and Physiology, Howard Hughes Medical Institute,
      Northwestern University, 2153 North Campus Drive, Evanston, Illinois, 60208-3520,
      USA.
FAU - King, D P
AU  - King DP
FAU - Zhao, Y
AU  - Zhao Y
FAU - Sangoram, A M
AU  - Sangoram AM
FAU - Du, F
AU  - Du F
FAU - Bowcock, A M
AU  - Bowcock AM
FAU - Moore, R Y
AU  - Moore RY
FAU - Takahashi, J S
AU  - Takahashi JS
LA  - eng
SI  - GENBANK/AF011568
GR  - R37MH39592/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genomics
JT  - Genomics
JID - 8800135
RN  - 0 (DNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - 0 (Trans-Activators)
RN  - EC 2.3.1.48 (CLOCK Proteins)
RN  - EC 2.3.1.48 (CLOCK protein, human)
RN  - EC 2.3.1.48 (Clock protein, mouse)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Blotting, Northern
MH  - CLOCK Proteins
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 4/genetics
MH  - Cloning, Molecular
MH  - DNA, Complementary/chemistry/genetics
MH  - Exons
MH  - Gene Expression
MH  - Genes/genetics
MH  - Genetic Variation
MH  - Humans
MH  - Hybrid Cells
MH  - In Situ Hybridization
MH  - Introns
MH  - Molecular Sequence Data
MH  - RNA, Messenger/analysis/genetics
MH  - Sequence Analysis, DNA
MH  - Sequence Homology, Amino Acid
MH  - Suprachiasmatic Nucleus/metabolism
MH  - Trans-Activators/*genetics
EDAT- 1999/04/13 00:00
MHDA- 1999/04/13 00:01
CRDT- 1999/04/13 00:00
PHST- 1999/04/13 00:00 [pubmed]
PHST- 1999/04/13 00:01 [medline]
PHST- 1999/04/13 00:00 [entrez]
AID - S0888-7543(98)95675-0 [pii]
AID - 10.1006/geno.1998.5675 [doi]
PST - ppublish
SO  - Genomics. 1999 Apr 15;57(2):189-200. doi: 10.1006/geno.1998.5675.