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. 2021 Oct 7;53(10):1529–1538. doi: 10.1038/s12276-021-00681-0

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — This autoregulatory feedback loop cycles between the CLOCK/BMAL1 transcriptional activator complex and its repressors (PER/CRY, REV-ERBα) or activators (RORα/β) to constitute the molecular clock oscillator that drives the expression of multiple clock-controlled genes (CCGs), such as metabolic genes, signaling genes, and epigenetic regulators.