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]