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

Mol Cell Biol. 2010 Dec;30(24):5636-48. doi: 10.1128/MCB.00781-10. Epub 2010 Oct 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics*
  • ARNTL Transcription Factors / metabolism*
  • Animals
  • Biological Clocks / physiology*
  • Cell Line
  • Chromatin Immunoprecipitation
  • Circadian Rhythm / physiology*
  • Computational Biology / methods
  • Energy Metabolism / genetics*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation*
  • Genome
  • High-Throughput Screening Assays / methods
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Microarray Analysis / methods

Substances

  • ARNTL Transcription Factors