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. 2022 Nov 18;9:886244. doi: 10.3389/fnut.2022.886244

Figure 2.

Figure 2

Clock genes and their transcription–translational feedback loops (TTFLs) at the cellular level (inside/outside the nucleus) in mammals. In the core loop, CLOCK and BMAL1 dimers bind to the E-box, promoting the expression of the Per and Cry genes and, in turn, inhibiting the CLOCK/BMAL1-dimer-dependent gene expression. In the stabilizing loop, the combination of the CLOCK/BMAL1 dimer and the E-box can activate the expression of RORα and REV-ERB. The accumulation of the REV-ERB molecule can inhibit the expression of the BMAL1 gene, while the accumulated RORα molecule can activate the expression of the BMAL1 gene (lower case italic characters and single wavy lines indicate mRNA). (+)/ → means activating gene expression; (–)/T means inhibiting gene expression.