Redundancy in circadian clocks? The transcription factor BMAL1 is a core component of the mammalian circadian clock; without it, circadian behaviors are abolished. However, Ray et al. found that in animals lacking BMAL1, peripheral tissues synchronized with a brief pulse of the glucocorticoid hormone dexamethasone appear to retain a 24-hour pacemaker that sustains rhythmic gene expression, protein abundance, and protein phosphorylation in excised liver cells and fibroblasts (see the Perspective by Brown and Sato). These oscillations persisted in the absence of cues from changes in light or temperature. The results raise intriguing questions about the possible nature of the oscillator that maintains the observed rhythms. Science, this issue p. 800; see also p. 740 Mouse liver and fibroblast cells retain 24-hour biochemical oscillations without a key circadian clock component. Circadian (~24 hour) clocks have a fundamental role in regulating daily physiology. The transcription factor BMAL1 is a principal driver of a molecular clock in mammals. Bmal1 deletion abolishes 24-hour activity patterning, one measure of clock output. We determined whether Bmal1 function is necessary for daily molecular oscillations in skin fibroblasts and liver slices. Unexpectedly, in Bmal1 knockout mice, both tissues exhibited 24-hour oscillations of the transcriptome, proteome, and phosphoproteome over 2 to 3 days in the absence of any exogenous drivers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. We suggest that such oscillations might be underpinned by transcriptional regulation by the recruitment of ETS family transcription factors, and nontranscriptionally by co-opting redox oscillations.

中文翻译：

---

缺乏时钟基因 Bmal1 时的昼夜节律


生物钟的冗余？转录因子 BMAL1 是哺乳动物生物钟的核心组成部分；没有它，昼夜节律行为就会被废除。然而，雷等人。发现在缺乏 BMAL1 的动物中，与糖皮质激素地塞米松短暂脉冲同步的外周组织似乎保留了 24 小时起搏器，维持切除的肝细胞和成纤维细胞中的节律性基因表达、蛋白质丰度和蛋白质磷酸化（参见 Perspective布朗和佐藤）。在没有光线或温度变化的提示的情况下，这些振荡持续存在。结果提出了关于维持观察到的节律的振荡器的可能性质的有趣问题。科学，本期第 14 页。 800；另见 p. 740 小鼠肝脏和成纤维细胞在没有关键生物钟成分的情况下保持 24 小时生化振荡。昼夜节律（~24 小时）时钟在调节日常生理机能方面发挥着重要作用。转录因子 BMAL1 是哺乳动物分子钟的主要驱动因素。 Bmal1 删除废除了 24 小时活动模式，这是时钟输出的一种衡量标准。我们确定了 Bmal1 功能对于皮肤成纤维细胞和肝脏切片的日常分子振荡是否是必需的。出乎意料的是，在 Bmal1 敲除小鼠中，在没有任何外源驱动因素（例如日常光照或温度循环）的情况下，两种组织都在 2 至 3 天内表现出转录组、蛋白质组和磷酸蛋白质组的 24 小时振荡。这表明 Bmal1 敲除中具有强大的 24 小时分子起搏器能力。我们认为，这种振荡可能是通过招募 ETS 家族转录因子进行转录调节，以及通过选择氧化还原振荡进行非转录调节来支撑的。