Drosophila CRYPTOCHROME is a circadian transcriptional repressor
Drosophila CRYPTOCHROME is a circadian transcriptional repressor
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DOI：
10.1016/j.cub.2006.01.034
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发表时间：
2006-03-07
期刊：
影响因子：
9.2
通讯作者：
Blau, J
中科院分区：
文献类型：
--
作者：
Collins, B;Mazzoni, EO;Blau, J
背景：虽然大多数生物钟成分在果蝇和哺乳动物之间是保守的，但隐花色素(CRY)蛋白的作用是非常不同的：果蝇的CRY蛋白是昼夜节律的光感受器，而哺乳动物的CRY蛋白(mCRY1和2)是转录抑制蛋白，对分子时钟振荡是必不可少的。我们发现，由转录因子Clock(CLK)和Cyc(Cyc)直接激活的基因的RNA水平在CRY(B)突变眼中被去抑制。反之，虽然在眼中过度表达CREY和Period(PER)抑制了CLK/CyC的活性，但PER和PER的单独表达都没有被抑制。果蝇哭声也能抑制细胞培养中CLK/CyC的活性。CREY的抑制似乎仅限于外周时钟，因为在起搏器神经元中，无论是CRAY(B)突变体还是PER和CREY的过度表达都不会对分子或行为节律产生显著影响。通过去除PER和CRY两个阻遏物来增加CLK/CyC的活性，导致永恒时钟基因的异位表达，类似于CLK本身的过度表达。结论：果蝇CRY是一种转录抑制物，是外周生物钟振荡和正确指定时钟细胞所必需的。
Background: Although most circadian clock components are conserved between Drosophila and mammals, the roles assigned to the CRYPTOCHROME (CRY) proteins are very different: Drosophila CRY functions as a circadian photoreceptor, whereas mammalian CRY proteins (mCRY1 and 2) are transcriptional repressors essential for molecular clock oscillations.Results: Here we demonstrate that Drosophila CRY also functions as a transcriptional repressor. We found that RNA levels of genes directly activated by the transcription factors CLOCK (CLK) and CYCLE (CYC) are derepressed in cry(b) mutant eyes. Conversely, while overexpression of CRY and PERIOD (PER) in the eye repressed CLK/CYC activity, neither PER nor CRY repressed individually. Drosophila CRY also repressed CLK/CYC activity in cell culture. Repression by CRY appears confined to peripheral clocks, since neither cry(b) mutants nor overexpression of PER and CRY together in pacemaker neurons significantly affected molecular or behavioral rhythms. Increasing CLK/CYC activity by removing two repressors, PER and CRY, led to ectopic expression of the timeless clock gene, similar to overexpression of Clk itself.Conclusions: Drosophila CRY functions as a transcriptional repressor required for the oscillation of peripheral circadian clocks and for the correct specification of clock cells.