Dual role of the CLOCK/BMAL1 circadian complex in transcriptional regulation

Mar 2, 2006FASEB journal : official publication of the Federation of American Societies for Experimental Biology

The CLOCK/BMAL1 circadian complex has two roles in controlling gene activity

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Abstract

The CLOCK/BMAL1 complex can suppress promoter activity through interaction with CRYPTOCHROME (CRY).

  • CLOCK/BMAL1 is known to positively regulate E-box containing promoters.
  • Interaction with CRY allows CLOCK/BMAL1 to also repress certain promoters.
  • This dual function helps explain unexpected circadian gene expression patterns in Bmal1 null mice.
  • The shift from activation to repression may enhance circadian gene expression control.
  • CLOCK/BMAL1 can disrupt the regulation of genes by non-circadian transcription factors like N-MYC and ETS.
  • Both repression and activation of gene transcription appear necessary for circadian responses to external stimuli, such as stress from anticancer treatment.

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