PMID- 10409723
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 8
DP  - 1999 Aug
TI  - PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1
      heterodimer without disrupting formation of the heterodimer: a basis for
      circadian transcription.
PG  - 5316-25
AB  - The Drosophila CLOCK (dCLOCK) and CYCLE (CYC) (also referred to as dBMAL1)
      proteins are members of the basic helix-loop-helix PAS (PER-ARNT-SIM) superfamily
      of transcription factors and are required for high-level expression of the
      circadian clock genes period (per) and timeless (tim). Several lines of evidence 
      indicate that PER, TIM, or a PER-TIM heterodimer somehow inhibit the
      transcriptional activity of a putative dCLOCK-CYC complex, generating a
      negative-feedback loop that is a core element of the Drosophila circadian
      oscillator. In this report we show that PER and/or TIM inhibits the binding of a 
      dCLOCK-CYC heterodimer to an E-box-containing DNA fragment that is present in the
      5' nontranscribed region of per and acts as a circadian enhancer element.
      Surprisingly, inhibition of this DNA binding activity by PER, TIM, or both is not
      accompanied by disruption of the association between dCLOCK and CYC. The results 
      suggest that the interaction of PER, TIM, or both with the dCLOCK-CYC heterodimer
      induces a conformational change or masks protein regions in the heterodimer,
      leading to a reduction in DNA binding activity. Together with other findings, our
      results strongly suggest that daily cycles in the association of PER and TIM with
      the dCLOCK-CYC complex probably contribute to rhythmic expression of per and tim.
FAU - Lee, C
AU  - Lee C
AD  - Graduate Program in Microbiology and Molecular Genetics, Rutgers University,
      Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey 08854,
      USA.
FAU - Bae, K
AU  - Bae K
FAU - Edery, I
AU  - Edery I
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (ARNTL Transcription Factors)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Clk protein, Drosophila)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Insect Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PER protein, Drosophila)
RN  - 0 (Period Circadian Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (cyc protein, Drosophila)
RN  - 0 (tim protein, Drosophila)
RN  - 9007-49-2 (DNA)
RN  - EC 2.3.1.48 (CLOCK Proteins)
SB  - IM
MH  - ARNTL Transcription Factors
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - CLOCK Proteins
MH  - Circadian Rhythm/genetics/*physiology
MH  - DNA/genetics/*metabolism
MH  - Dimerization
MH  - *Drosophila Proteins
MH  - Drosophila melanogaster/*genetics
MH  - Enhancer Elements, Genetic
MH  - Feedback
MH  - *Gene Expression Regulation
MH  - Genes, Insect
MH  - Helix-Loop-Helix Motifs/*physiology
MH  - Insect Proteins/biosynthesis/chemistry/genetics/*physiology
MH  - Multigene Family
MH  - Nuclear Proteins/biosynthesis/genetics/*physiology
MH  - Period Circadian Proteins
MH  - Protein Multimerization
MH  - RNA, Messenger/biosynthesis
MH  - Trans-Activators/chemistry/*physiology
MH  - Transcription Factors/*antagonists & inhibitors/chemistry/physiology
MH  - *Transcription, Genetic
PMC - PMC84375
EDAT- 1999/07/20 00:00
MHDA- 1999/07/20 00:01
CRDT- 1999/07/20 00:00
PHST- 1999/07/20 00:00 [pubmed]
PHST- 1999/07/20 00:01 [medline]
PHST- 1999/07/20 00:00 [entrez]
AID - 10.1128/MCB.19.8.5316 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Aug;19(8):5316-25. doi: 10.1128/MCB.19.8.5316.