title: Non-circadian expression masking clock-driven weak transcription rhythms in U2OS cells.
abstract: U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate with detectable rhythmic transcript levels. Luciferase fusions reveal that the circadian clock supports robust but low amplitude transcription rhythms of representative promoters. However, rhythmic transcription of these potentially clock-controlled genes is masked by non-circadian transcription that overwrites the weaker contribution of the clock in constant conditions. Our data suggest that U2OS cells harbor an intrinsically rather weak circadian oscillator. The oscillator has the potential to regulate a large number of genes. The contribution of circadian versus non-circadian transcription is dependent on the metabolic state of the cell and may determine the apparent complexity of the circadian transcriptome.
authors.affiliation: Biochemistry Center, University of Heidelberg, Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoffmann
authors.affiliation: Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Symul
authors.affiliation: Biochemistry Center, University of Heidelberg, Heidelberg, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Shostak
authors.affiliation: Biochemistry Center, University of Heidelberg, Heidelberg, Germany.
authors.forename: Tamás
authors.initials: T
authors.lastname: Fischer
authors.affiliation: Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Naef
authors.affiliation: Biochemistry Center, University of Heidelberg, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Brunner
mesh_terms: D056930:ARNTL Transcription Factors / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D056926:CLOCK Proteins / Q000737:chemistry* / Q000235:genetics; D045744:Cell Line, Tumor; D057906:Circadian Clocks; D056931:Cryptochromes / Q000737:chemistry* / Q000235:genetics; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D011401:Promoter Regions, Genetic
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; C538963:CRY1 protein, human; D056931:Cryptochromes; D056926:CLOCK Proteins; C538943:CLOCK protein, human