C-terminal binding protein (CtBP) activates the expression of E-box clock genes with CLOCK/CYCLE in Drosophila

In Drosophila, CLOCK/CYCLE heterodimer (CLK/CYC) is the primary activator of circadian clock genes that contain the E-box sequence in their promoter regions (hereafter referred to as "E-box clock genes"). Although extensive studies have investigated the feedback regulation of clock genes,...

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Bibliographic Details
Published in:PloS one 2013-04, Vol.8 (4), p.e63113-e63113
Main Authors: Itoh, Taichi Q, Matsumoto, Akira, Tanimura, Teiichi
Format: Article
Language:English
Subjects:
Alcohol Oxidoreductases - genetics
Alcohol Oxidoreductases - metabolism
Amino acids
Animals
ARNTL Transcription Factors - chemistry
ARNTL Transcription Factors - genetics
Binding
Biological Clocks - genetics
Biology
Circadian rhythm
Circadian Rhythm - genetics
Circadian rhythms
CLOCK Proteins - chemistry
CLOCK Proteins - genetics
Cobalt
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Drosophila
Drosophila - genetics
Drosophila - metabolism
Drosophila Proteins - chemistry
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
E-Box Elements
Female
Gene Expression
Gene Expression Regulation
Gene Knockdown Techniques
Gene regulation
Genes
Genomics
Insects
Life sciences
Male
Metabolism
NAD
Neurosciences
Physiology
Protein Multimerization
Proteins
Transcription activation
Transcription, Genetic
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Summary:In Drosophila, CLOCK/CYCLE heterodimer (CLK/CYC) is the primary activator of circadian clock genes that contain the E-box sequence in their promoter regions (hereafter referred to as "E-box clock genes"). Although extensive studies have investigated the feedback regulation of clock genes, little is known regarding other factors acting with CLK/CYC. Here we show that Drosophila C-terminal binding protein (dCtBP), a transcriptional co-factor, is involved in the regulation of the E-box clock genes. In vivo overexpression of dCtBP in clock cells lengthened or abolished circadian locomotor rhythm with up-regulation of a subset of the E-box clock genes, period (per), vrille (vri), and PAR domain protein 1ε (Pdp1ε). Co-expression of dCtBP with CLK in vitro also increased the promoter activity of per, vri, Pdp1ε and cwo depending on the amount of dCtBP expression, whereas no effect was observed without CLK. The activation of these clock genes in vitro was not observed when we used mutated dCtBP which carries amino acid substitutions in NAD+ domain. These results suggest that dCtBP generally acts as a putative co-activator of CLK/CYC through the E-box sequence.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0063113