title: Timing of circadian genes in mammalian tissues.
abstract: Circadian clocks are endogenous oscillators driving daily rhythms in physiology. The cell-autonomous clock is governed by an interlocked network of transcriptional feedback loops. Hundreds of clock-controlled genes (CCGs) regulate tissue specific functions. Transcriptome studies reveal that different organs (e.g. liver, heart, adrenal gland) feature substantially varying sets of CCGs with different peak phase distributions. To study the phase variability of CCGs in mammalian peripheral tissues, we develop a core clock model for mouse liver and adrenal gland based on expression profiles and known cis-regulatory sites. 'Modulation factors' associated with E-boxes, ROR-elements, and D-boxes can explain variable rhythms of CCGs, which is demonstrated for differential regulation of cytochromes P450 and 12 h harmonics. By varying model parameters we explore how tissue-specific peak phase distributions can be generated. The central role of E-boxes and ROR-elements is confirmed by analysing ChIP-seq data of BMAL1 and REV-ERB transcription factors.
authors.affiliation: 1] Institute for Theoretical Biology, 10115 Berlin, Germany [2] Centre for Functional Genomics and Biochips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Anja
authors.initials: A
authors.lastname: Korenčič
authors.affiliation: 1] Centre for Functional Genomics and Biochips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia [2] Diagenomi Ltd, 1000 Ljubljana, Slovenia.
authors.forename: Rok
authors.initials: R
authors.lastname: Košir
authors.affiliation: Institute for Theoretical Biology, 10115 Berlin, Germany.
authors.forename: Grigory
authors.initials: G
authors.lastname: Bordyugov
authors.affiliation: Institute for Theoretical Biology, 10115 Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Lehmann
authors.affiliation: Centre for Functional Genomics and Biochips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Damjana
authors.initials: D
authors.lastname: Rozman
authors.affiliation: Institute for Theoretical Biology, 10115 Berlin, Germany.
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Herzel
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000502:physiology*; D057906:Circadian Clocks; D005786:Gene Expression Regulation; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D017440:Photoperiod; D014158:Transcription, Genetic
chemical_list: D056926:CLOCK Proteins