Identification of a new clock-related element EL-box involved in circadian regulation by BMAL1/CLOCK and HES1

In silico analysis identified 10 sequence motifs correlated with circadian phases of gene expression in cartilage.

• One identified motif, the E-box-like clock-related element (EL-box), can mediate transcription induced by BMAL1/CLOCK.
• Expression of genes containing the EL-box, such as Ank, Dbp, and Nr1d1, was induced by BMAL1/CLOCK or BMAL1/NPAS2.
• The responsiveness of EL-box elements to DEC1 and DEC2's suppressive actions is less potent compared to the E-box.
• HES1 suppressed the enhancer activity of the EL-box but did not affect the E-box.
• An EL-box in the Dbp promoter cooperated with a noncanonical E-box to mediate BMAL1/CLOCK actions.
• These findings indicate that the EL-box may play a role in the circadian regulation of clock and clock-controlled genes.

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