A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation
A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation
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DOI：
10.1016/j.bbrc.2003.11.099
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发表时间：
2004-01-02
影响因子：
3.1
通讯作者：
Kato, Y
中科院分区：
文献类型：
--
作者：
Kawamoto, T;Noshiro, M;Kato, Y
与生物钟基因Per（s）的转录相关的自反馈环被普遍认为是昼夜节律产生的分子机制，其中CLOCK/BMAL起正调节作用，PER/CRY起负调节作用。我们在这里展示了Dec 1的一个自反馈环，它编码一个基本的螺旋-环-螺旋转录因子：CLOCK/BMAL增加了Dec 1的启动子活性，而DEC 1和DEC 2以及PER和PER抑制了诱导的表达。三个CACGTG E-box负责Dec 1转录的激活和抑制。Clock/Bmal的强制表达增加内源性Dec 1 mRNA水平，并且Dec 1的过表达导致Dec 2、Per 2和Dbp表达的抑制。Clock/Clock突变小鼠心脏中Dec 1的表达水平全天持续较低。这些发现表明，Dec 1是积极调节的时钟/BMAL，并参与昼夜节律的调节，通过抑制时钟/BMAL诱导的基因表达。在某些情况下，Dec 1的自动反馈回路可能与Per的核心反馈回路互锁。(C)2003年爱思唯尔公司All rights reserved.
An autofeedback loop associated with transcription of clock gene(s), Per(s), is generally accepted as the molecular machinery of circadian rhythm generation, in which CLOCK/BMAL act as positive regulators and PER/CRY as negative ones. We show here an autofeedback loop of Dec1 encoding a basic helix-loop-helix transcription factor: CLOCK/BMAL increased the promoter activity of Dec1, and DEC1 and DEC2 as well as PERs and CRYs suppressed the induced expression. Three CACGTG E-boxes are responsible for both the activation and the suppression of Dec1 transcription. Forced expression of Clock/Bmal increased endogenous Dec1 mRNA level, and overexpression of Dec1 resulted in suppression of Dec2, Per2, and Dbp expression. The level of Dec1 expression in the heart of Clock/Clock mutant mice was continuously low throughout the day. These findings suggest that Dec1 is positively regulated by CLOCK/BMAL and is involved in circadian rhythm regulation by suppressing CLOCK/BMAL-induced gene expression. The autofeedback loop of Dec1 may be interlocked with the core feedback loop of Per in some situations. (C) 2003 Elsevier Inc. All rights reserved.