Tandem association of CLOCK:BMAL1 complexes on DNA enables recruitment of CBP/p300 through multivalent interactions.

Sep 15, 2025bioRxiv : the preprint server for biology

Back-to-back binding of CLOCK and BMAL1 proteins on DNA helps attract CBP/p300 through multiple interactions

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Abstract

The presence of tandem E-boxes enables CLOCK:BMAL1 to bind more effectively within nucleosomes.

  • CLOCK:BMAL1 interacts with E-box motifs to regulate gene expression in a circadian rhythm of approximately 24 hours.
  • Tandem arrangements of E-boxes are crucial for maintaining robust oscillations of core clock genes.
  • Binding to internal sites on the nucleosome allows CLOCK:BMAL1 to release DNA from the histone core.
  • This release presents multiple binding sites for the coactivator CBP/p300, facilitating multivalent interactions.
  • Deletion of specific domains in CBP or inhibiting its interactions leads to a significant reduction in CLOCK:BMAL1 activity.
  • Multivalent interactions with CBP may be important for the recruitment of this cofactor by CLOCK:BMAL1 in cellular contexts.

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