The mammalian circadian clock is composed of an autoregulatory network in which the BMAL1, CLOCK, NPAS2, PER and CRY transcription factors interact in transcriptional feedback loops. Although it is known that the circadian clock regulates the expression of thousands of transcripts, Joseph Takahashi and colleagues now report the genome-wide architecture of the transcriptional network regulated by the circadian clock in mammals (Science 338, 349–354, 2012). The authors used chromatin immunoprecipitation sequencing (ChIP-seq) to profile the DNA binding of BMAL1, CLOCK, NPAS2, PER1, PER2, CRY1, CRY2, RNA polymerase 2, p300 and CBP throughout the circadian cycle in mouse liver. They also measured gene expression with RNA sequencing. They found circadian-dependent binding of transcription factors and RNA polymerase 2 and circadian-dependent variation in RNA expression. They also profiled the histone modifications H3K4me1, H3K4me3, H3K9ac, H3K27ac, H3K36me3 and H3K79me2 across the genome throughout the circadian cycle using ChIP-seq. They found strong circadian-dependent patterns of RNA polymerase 2 recruitment and H3K4me3, H3K9ac and H3K27ac occupancy at transcriptional start sites, also finding evidence for circadian-dependent histone modifications at the majority of expressed genes.