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. Author manuscript; available in PMC: 2017 Jul 5.
Published in final edited form as: Nat Struct Mol Biol. 2016 Dec 6;23(12):1045–1052. doi: 10.1038/nsmb.3324

Figure 2. Mechanisms regulating genomic binding of circadian TFs.

Figure 2

(a) Competitive binding among different TFs is observed at E-box, RORE, and D-box motifs. TF binding to the E-box motif, including DEC1/2, USF1, HES1, MYC can inhibit BMAL1 binding. Circadian expressed Rev-erbα competes with RORα, which results in oscillation of RORα binding. E4BP4 competes with other PAR-domain basic leucine zipper TFs DBP/TEF/HLF, which also leads to a robust diurnal switch on/off of their target gene transcription. (b) BMAL1 and CLOCK can function as pioneer TFs to promote the chromatin de-condensation during activation phase. Similarly, RORα could also recruit epigenetic modification machinery to remodel the chromatin structure to facilitate the binding of Rev-erbα. (c) PXDLS peptide motif, which is conserved in CBP, RIP140 and Rev-erbα, can interact with BMAL1/CLOCK and regulate circadian transcription. On the other hand, Rev-erbα can also be tethered to lineage determining TFs, such as HNF6 in the liver, to regulate different metabolic output processes in various tissues.