Max Planck Research Group "Sleep and Waking", Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.
Institute of Neurobiology, University of Lübeck, 23562, Germany.
Genetics. 2020 Nov;216(3):735-752. doi: 10.1534/genetics.120.303533. Epub 2020 Aug 7.
Sleep is a conserved behavioral state. Invertebrates typically show quiet sleep, whereas in mammals, sleep consists of periods of nonrapid-eye-movement sleep (NREMS) and REM sleep (REMS). We previously found that the transcription factor AP-2 promotes sleep in and In mammals, several paralogous AP-2 transcription factors exist. Sleep-controlling genes are often conserved. However, little is known about how sleep genes evolved from controlling simpler types of sleep to govern complex mammalian sleep. Here, we studied the roles of and in sleep control in mice. Consistent with our results from and , the AP-2 transcription factors and also control sleep in mice. Surprisingly, however, the two AP-2 paralogs play contrary roles in sleep control. reduction of function causes stronger delta and theta power in both baseline and homeostasis analysis, thus indicating increased sleep quality, but did not affect sleep quantity. By contrast, reduction of function decreased NREM sleep time specifically during the dark phase, reduced NREMS and REMS power, and caused a weaker response to sleep deprivation. Consistent with the observed signatures of decreased sleep quality, stress resistance and memory were impaired in mutant animals. Also, the circadian period was slightly shortened. Taken together, AP-2 transcription factors control sleep behavior also in mice, but the role of the genes functionally diversified to allow for a bidirectional control of sleep quality. Divergence of AP-2 transcription factors might perhaps have supported the evolution of more complex types of sleep.
睡眠是一种保守的行为状态。无脊椎动物通常表现出安静的睡眠，而在哺乳动物中，睡眠由非快速眼动睡眠（NREMS）和快速眼动睡眠（REMS）组成。我们之前发现转录因子 AP-2 促进了 和 的睡眠。在哺乳动物中，存在几种类似的 AP-2 转录因子。控制睡眠的基因通常是保守的。然而，关于睡眠基因如何从控制更简单类型的睡眠演变为控制复杂的哺乳动物睡眠知之甚少。在这里，我们研究了 AP-2 转录因子 在控制小鼠睡眠中的作用。与我们从 和 中得到的结果一致，AP-2 转录因子 和 也控制着小鼠的睡眠。然而，令人惊讶的是，这两种 AP-2 同源物在睡眠控制中起着相反的作用。 功能降低导致基线和自主分析中 delta 和 theta 功率更强，从而表明睡眠质量提高，但不影响睡眠量。相比之下， 功能降低会特异性地减少黑暗期的 NREM 睡眠时间，降低 NREMS 和 REMS 功率，并导致对睡眠剥夺的反应减弱。与观察到的睡眠质量下降的特征一致， 突变动物的应激抗性和记忆受损。此外，昼夜节律周期略有缩短。总之，AP-2 转录因子也控制着小鼠的睡眠行为，但 基因的功能多样化，允许对睡眠质量进行双向控制。AP-2 转录因子的分化可能支持了更复杂类型睡眠的进化。
