Helix-loop-helix Protein Id2 Stabilizes Mammalian Circadian Oscillation Under Constant Light Conditions

The mammalian circadian oscillator is composed of interacting positive and negative transcription events. The clock proteins PER1 and PER2 play essential roles in a negative limb of the feedback loop that generates the circadian rhythm in mammals. In addition, the proteins CLOCK and BMAL1 (also known as ARNTL) form a heterodimer that drives the Per genes via the E-box consensus sequences within their promoter regions. In the present study, we demonstrate that Id2 is involved in stabilization of the amplitudes of the circadian oscillations by suppressing transcriptional activation of clock genes Clock and Bmal1. Id2 shows dynamic oscillation in the SCN, with a peak in the late subjective night. Under constant dark conditions (DD), Id2(-/-) mice showed no apparent difference in locomotor activity, however, under constant light conditions (LL), Id2(-/-) mice exhibit aberrant locomotor activity, with lower circadian oscillation amplitudes, although the free running periods in Id2(-/-) mice show no differences from those in either wild type or heterozygous mice. Id2(-/-) animals also exhibit upregulation of Per1 in constant light, during both the subjective night and day. In wild type mice, Id2 is upregulated by constant light exposure during the subjective night. We propose that Id2 expression in the SCN contributes to maintenance of dynamic circadian oscillations.

哺乳动物的生物钟振荡器由相互作用的正负转录事件组成。时钟蛋白PER1和PER2在产生哺乳动物昼夜节律的反馈回路的负向环节中起着关键作用。此外，蛋白质CLOCK和BMAL1（也称为ARNTL）形成异二聚体，通过其启动子区域内的E - box共有序列驱动Per基因。在本研究中，我们证明Id2通过抑制时钟基因Clock和Bmal1的转录激活参与稳定昼夜节律振荡的幅度。Id2在视交叉上核（SCN）中呈现动态振荡，在主观夜晚后期达到峰值。在恒定黑暗条件（DD）下，Id2（ - / - ）小鼠的运动活动没有明显差异；然而，在恒定光照条件（LL）下，Id2（ - / - ）小鼠表现出异常的运动活动，昼夜节律振荡幅度较低，尽管Id2（ - / - ）小鼠的自由运行周期与野生型或杂合型小鼠没有差异。Id2（ - / - ）动物在恒定光照下的主观夜晚和白天也表现出Per1的上调。在野生型小鼠中，Id2在主观夜晚因持续光照而被上调。我们提出视交叉上核中的Id2表达有助于维持动态的昼夜节律振荡。