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      Transcriptional architecture and chromatin landscape of the core circadian clock in mammals.

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          Abstract

          The mammalian circadian clock involves a transcriptional feed back loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression, and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases: a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Only 22% of messenger RNA (mRNA) cycling genes are driven by de novo transcription, suggesting that both transcriptional and posttranscriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling.

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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          Oct 19 2012
          : 338
          : 6105
          Affiliations
          [1 ] Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
          Article
          science.1226339 NIHMS483327
          10.1126/science.1226339
          3694775
          22936566
          3c79f681-9683-4fc7-9434-8f28b45b97dd
          History

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