Execution of the circadian negative feedback loop in Neurospora requires the ATP-dependent chromatin-remodeling enzyme CLOCKSWITCH
Execution of the circadian negative feedback loop in Neurospora requires the ATP-dependent chromatin-remodeling enzyme CLOCKSWITCH
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DOI：
10.1016/j.molcel.2007.01.010
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发表时间：
2007-02-23
期刊：
影响因子：
16
通讯作者：
Dunlap, Jay C.
中科院分区：
文献类型：
--
作者：
Belden, William J.;Loros, Jennifer J.;Dunlap, Jay C.
在神经孢子虫的昼夜节律系统中，转录因子White -1 （WC-1）和White - Collar-2 （WC-2）激活frq的表达，而frq的基因产物抑制frq自身的表达。WC蛋白被认为形成专性复合体；然而，染色质免疫沉淀（ChIP）表明，WC-2以有节奏的方式与frq启动子结合，而WC-1是连续结合的。在昼夜周期中检测到组蛋白乙酰化的小振荡，在光诱导激活后显着减少。核酸酶可及性实验表明在frq启动子处染色质重排；因此，删除了19个与atp依赖性染色质重塑酶同源的基因，并检测了菌株的时钟表型。时钟功能需要一个基因，称为时钟开关（csw-1）；其产物定位于FRQ启动子，是FRQ正确表达所必需的，并且对染色质结构有影响。这些数据表明，CSW-1调控启动子DNA的可及性，从而产生从转录活性到抑制状态的急剧转变。
In the Neurospora circadian system, the transcription factors White Collar-1 (WC-1) and White Collar-2 (WC-2) activate expression of frq, whose gene product inhibits its own expression. The WC proteins are thought to form an obligate complex; however, chromatin immunoprecipitation (ChIP) indicates that WC-2 binds to the frq promoter in a rhythmic fashion, whereas WC-1 is bound continuously. Small oscillations in histone acetylation are detected over the circadian cycle with a marked reduction upon light-induced activation. Nuclease accessibility experiments indicate chromatin rearrangement at the frq promoter; therefore, 19 genes with homology to ATP-dependent chromatin-remodeling enzymes were deleted and the strains examined for clock phenotypes. One gene, designated clockswitch (csw-1), is required for clock function; its product localizes to the frq promoter, is required for proper frq expression, and has an impact on chromatin structure. The data suggest that CSW-1 regulates accessibility of promoter DNA, thus generating the sharp transition from the transcriptionally active to the repressed state.