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. 2021 Feb 17;18:8. doi: 10.1186/s12976-021-00139-w

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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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Core clock protein levels, relative to their peak values. The peaks of cytosolic PER (P₁) and cytosolic CRY (C) (dashed gray curves in panels a and b) follow shortly after the peaks of BMAL1-CLOCK (BC) (solid purple curve in panel d). The delays between P₁ and nuclear PER (P_N), and between C and nuclear CRY (C_N), are around 9 hours (Panels a and b). P_N and C_N reach maximum expression at the beginning of dark, consistent with experimental data [38]. P_N and C_N bind and form nuclear PER-CRY (PC_N), which inhibits BC through sequestration. Thus, when PC_N peaks at 12 hours Zeitgeber time (ZT12), the expression levels of P₁ and C are significantly reduced. Additionally, C_N directly inhibits the production of P₁ and C during night, as proposed in [17]