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