Genome-wide profiling of the core clock protein BMAL1 targets reveals a strict relationship with metabolism

F. Hatanaka, C. Matsubara, J. Myung, T. Yoritaka, N. Kamimura, S. Tsutsumi, A. Kanai, Y. Suzuki, P. Sassone-Corsi, H. Aburatani, S. Sugano, T. Takumi

Research output: Contribution to journalArticlepeer-review

114 Citations (Scopus)


Circadian rhythms are common to most organisms and govern much of homeostasis and physiology. Since a significant fraction of the mammalian genome is controlled by the clock machinery, understanding the genome-wide signaling and epigenetic basis of circadian gene expression is essential. BMAL1 is a critical circadian transcription factor that regulates genes via E-box elements in their promoters. We used multiple high-throughput approaches, including chromatin immunoprecipitation-based systematic analyses and DNA microarrays combined with bioinformatics, to generate genome-wide profiles of BMAL1 target genes. We reveal that, in addition to E-boxes, the CCAATG element contributes to elicit robust circadian expression. BMAL1 occupancy is found in more than 150 sites, including all known clock genes. Importantly, a significant proportion of BMAL1 targets include genes that encode central regulators of metabolic processes. The database generated in this study constitutes a useful resource to decipher the network of circadian gene control and its intimate links with several fundamental physiological functions. © 2010, American Society for Microbiology.
Original languageEnglish
Pages (from-to)5636-5648
Number of pages13
JournalMolecular and Cellular Biology
Issue number24
Publication statusPublished - 2010


  • transcription factor ARNTL
  • animal
  • article
  • Bagg albino mouse
  • biological rhythm
  • biology
  • cell line
  • chromatin immunoprecipitation
  • circadian rhythm
  • energy metabolism
  • gene expression profiling
  • gene expression regulation
  • genetics
  • genome
  • high throughput screening
  • male
  • metabolism
  • methodology
  • microarray analysis
  • mouse
  • mouse mutant
  • physiology
  • Animals
  • ARNTL Transcription Factors
  • Biological Clocks
  • Cell Line
  • Chromatin Immunoprecipitation
  • Circadian Rhythm
  • Computational Biology
  • Energy Metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome
  • High-Throughput Screening Assays
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Microarray Analysis


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