Functional role of CREB-binding protein in the circadian clock system of Drosophila melanogaster.
Rhythmic histone acetylation underlies the oscillating expression of clock genes in the mammalian circadian clock system. Cellular factors that contain histone acetyltransferase and histone deacetylase activity have been implicated in these processes by direct interactions with clock genes, but their functional relevance remains to be assessed by use of appropriate animal models. Here, using transgenic fly models, we show that CREB-binding protein (CBP) participates in the transcriptional regulation of the Drosophila CLOCK/CYCLE (dCLK/CYC) heterodimer. CBP knockdown in pigment dispersing factor-expressing cells lengthens the period of adult locomotor rhythm with the prolonged expression of period and timeless genes, while CBP overexpression in timeless-expressing cells causes arrhythmic circadian behaviors with the impaired expression of these dCLK/CYC-induced clock genes. In contrast to the mammalian circadian clock system, CBP overexpression attenuates the transcriptional activity of the dCLK/CYC heterodimer in cultured cells, possibly by targeting the PER-ARNT-SIM domain of dCLK. Our data suggest that the Drosophila circadian clock system has evolved a distinct mechanism to tightly regulate the robust transcriptional potency of the dCLK/CYC heterodimer.
Lim
Chunghun
C
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Lee
Jongbin
J
Choi
Changtaek
C
Kim
Juwon
J
Doh
Eunjin
E
Choe
Joonho
J
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics; D001522:Behavior, Animal; D001683:Biological Clocks / Q000502:physiology*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D017344:Genes, Insect; D007814:Larva / Q000166:cytology; D009043:Motor Activity; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D050882:CREB-Binding Protein; D029721:Drosophila Proteins; C112805:cyc protein, Drosophila