美国宾夕法尼亚大学Akhilesh B. Reddy发现，时钟基因Bmal1缺失后仍存在昼夜节律。这一研究成果于2020年2月14日发表在国际学术期刊《科学》上。

研究人员验证了Bmal1功能对于皮肤成纤维细胞和肝脏切片中的日常分子振荡是否必要。出乎意料的是，在Bmal1基因敲除小鼠中，在没有任何外源性驱动因素（例如日常光照或温度循环）的情况下，这两个组织在2至3天内都表现出转录组、蛋白质组和磷酸化蛋白质组的24小时振荡。这表明Bmal1敲除个体中有其他调控24小时节律的分子机器。研究人员认为，这种周期振荡可能是由ETS家族转录因子的招募介导的转录调控所引起的，而非转录调节则是通过氧化还原振荡来引起的。

据了解，昼夜节律（约24小时）在调节日常生理中起着基本作用。转录因子BMAL1是哺乳动物中分子钟的主要驱动因子。Bmal1敲除影响了24小时活动模式（节律的一种度量方式）。

附：英文原文

Title: Circadian rhythms in the absence of the clock gene Bmal1

Author: Sandipan Ray, Utham K. Valekunja, Alessandra Stangherlin, Steven A. Howell, Ambrosius P. Snijders, Gopinath Damodaran, Akhilesh B. Reddy

Issue&Volume: 2020/02/14

Abstract: 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.

DOI: 10.1126/science.aaw7365

Source: https://science.sciencemag.org/content/367/6479/800