regulation of clock-controlled genes in mammalsclock-controlled调节基因在哺乳动物.pdfVIP

Regulation of Clock-Controlled Genes in Mammals 1,2. ´ 2. 3 4 5 Katarzyna Bozek , Angela Relogio , Szymon M. Kielbasa , Markus Heine , Christof Dame , Achim 4 2 Kramer , Hanspeter Herzel * ¨ 1 Max Planck Institute for Informatics, Saarbrucken, Germany, 2 Institute for Theoretical Biology, Humboldt University, Berlin, Germany, 3 Max Planck Institute for ´ ¨ Molecular Genetics, Berlin, Germany, 4 Laboratory of Chronobiology, Charite - Universitasmedizin Berlin, Berlin, Germany, 5 Department of Neonatology, Campus Virchow- ´ ¨ Klinikum Charite - Universitatsmedizin Berlin, Berlin, Germany Abstract The complexity of tissue- and day time-specific regulation of thousands of clock-controlled genes (CCGs) suggests that many regulatory mechanisms contribute to the transcriptional output of the circadian clock. We aim to predict these mechanisms using a large scale promoter analysis of CCGs. Our study is based on a meta-analysis of DNA-array data from rodent tissues. We searched in the promoter regions of 2065 CCGs for highly overrepresented transcription factor binding sites. In order to compensate the relatively high GC-content of CCG promoters, a novel background model to avoid a bias towards GC-rich motifs was employed. We found that many of the transcription factors with overrepresented binding sites in CCG promoters exhibit themselves circadian rhythms. Among the predicted factors are known regulators such as CLOCK:BMAL1, DBP, HLF,