title: C-terminal binding protein (CtBP) activates the expression of E-box clock genes with CLOCK/CYCLE in Drosophila.
abstract: 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.
authors: Graduate School of Systems Life Sciences, Kyushu University, Hakozaki, Fukuoka, Japan.
authors: Taichi Q
authors: TQ
authors: Itoh
authors: Akira
authors: A
authors: Matsumoto
authors: Teiichi
authors: T
authors: Tanimura
mesh_terms: D056930:ARNTL Transcription Factors / Q000737:chemistry / Q000235:genetics*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D056926:CLOCK Proteins / Q000737:chemistry / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D024721:E-Box Elements; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008297:Male; D055503:Protein Multimerization; D014158:Transcription, Genetic
chemical_list: D056930:ARNTL Transcription Factors; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112805:cyc protein, Drosophila; C096445:tim protein, Drosophila; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D056926:CLOCK Proteins
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