title: Drosophila CLOCK target gene characterization: implications for circadian tissue-specific gene expression.
abstract: CLOCK (CLK) is a master transcriptional regulator of the circadian clock in Drosophila. To identify CLK direct target genes and address circadian transcriptional regulation in Drosophila, we performed chromatin immunoprecipitation (ChIP) tiling array assays (ChIP-chip) with a number of circadian proteins. CLK binding cycles on at least 800 sites with maximal binding in the early night. The CLK partner protein CYCLE (CYC) is on most of these sites. The CLK/CYC heterodimer is joined 4-6 h later by the transcriptional repressor PERIOD (PER), indicating that the majority of CLK targets are regulated similarly to core circadian genes. About 30% of target genes also show cycling RNA polymerase II (Pol II) binding. Many of these generate cycling RNAs despite not being documented in prior RNA cycling studies. This is due in part to different RNA isoforms and to fly head tissue heterogeneity. CLK has specific targets in different tissues, implying that important CLK partner proteins and/or mechanisms contribute to gene-specific and tissue-specific regulation.
authors.affiliation: Howard Hughes Medical Institute, National Center for Behavioral Genomics, Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Katharine Compton
authors.initials: KC
authors.lastname: Abruzzi
authors.forename: Joseph
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Menet
authors.forename: Jennifer
authors.initials: J
authors.lastname: Desrochers
authors.forename: Abigail
authors.initials: A
authors.lastname: Zadina
authors.forename: Weifei
authors.initials: W
authors.lastname: Luo
authors.forename: Sasha
authors.initials: S
authors.lastname: Tkachev
authors.forename: Michael
authors.initials: M
authors.lastname: Rosbash
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics*; D004257:DNA Polymerase II / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D056950:Period Circadian Proteins / Q000378:metabolism; D011485:Protein Binding
chemical_list: D056930:ARNTL Transcription Factors; C120526:Clk protein, Drosophila; D029721:Drosophila Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; C112805:cyc protein, Drosophila; D056926:CLOCK Proteins; D004257:DNA Polymerase II
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