哺乳动物昼夜节律自动调节环路：一个timeless直系同源物与mPer1相互作用并负向调节CLOCK-BMAL1诱导的转录。

Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription.

作者信息

Sangoram A M, Saez L, Antoch M P, Gekakis N, Staknis D, Whiteley A, Fruechte E M, Vitaterna M H, Shimomura K, King D P, Young M W, Weitz C J, Takahashi J S

机构信息

Department of Neurobiology and Physiology and National Science Foundation, Center for Biological Timing, The Rockefeller University, New York, New York 10021, USA.

出版信息

Neuron. 1998 Nov;21(5):1101-13. doi: 10.1016/s0896-6273(00)80627-3.

DOI:10.1016/s0896-6273(00)80627-3

PMID:9856465

Abstract

We report the cloning and mapping of mouse (mTim) and human (hTIM) orthologs of the Drosophila timeless (dtim) gene. The mammalian Tim genes are widely expressed in a variety of tissues; however, unlike Drosophila, mTim mRNA levels do not oscillate in the suprachiasmatic nucleus (SCN) or retina. Importantly, hTIM interacts with the Drosophila PERIOD (dPER) protein as well as the mouse PER1 and PER2 proteins in vitro. In Drosophila (S2) cells, hTIM and dPER interact and translocate into the nucleus. Finally, hTIM and mPER1 specifically inhibit CLOCK-BMAL1-induced transactivation of the mPer1 promoter. Taken together, these results demonstrate that mTim and hTIM are mammalian orthologs of timeless and provide a framework for a basic circadian autoregulatory loop in mammals.

摘要

我们报道了果蝇无时间基因（dtim）的小鼠（mTim）和人类（hTIM）直系同源基因的克隆及定位。哺乳动物的Tim基因在多种组织中广泛表达；然而，与果蝇不同，mTim mRNA水平在视交叉上核（SCN）或视网膜中并无振荡现象。重要的是，hTIM在体外可与果蝇周期蛋白（dPER）以及小鼠PER1和PER2蛋白相互作用。在果蝇（S2）细胞中，hTIM和dPER相互作用并转位至细胞核。最后，hTIM和mPER1特异性抑制CLOCK-BMAL1诱导的mPer1启动子的反式激活。综上所述，这些结果表明mTim和hTIM是无时间基因的哺乳动物直系同源基因，并为哺乳动物中的基本昼夜节律自动调节环路提供了一个框架。