A Global Circadian Repressor Controls Antiphasic Expression of Metabolic Genes in Neurospora
A Global Circadian Repressor Controls Antiphasic Expression of Metabolic Genes in Neurospora
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DOI：
10.1016/j.molcel.2011.10.019
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发表时间：
2011-12-09
期刊：
影响因子：
16
通讯作者：
Brunner, Michael
中科院分区：
文献类型：
--
作者：
Sancar, Gencer;Sancar, Cigdem;Brunner, Michael
白领复合体(WCC)是脉孢子虫生物钟的核心转录因子，它激活转录抑制因子CSP1的早晨特异性表达。新合成的CSP1与辅阻遏子RCM1/RCO1和泛素连接酶UBR1以瞬时复合体形式存在。CSP1通过UBR1及其泛素结合酶RAD6被迅速过度磷酸化和降解。由CSP1控制的基因在晚上有节奏地表达并达到高峰(即，在与WCC直接控制的早晨特异的基因相反的阶段)。这些第二层基因的节律性表达主要依赖于CSP1的磷酸化和快速周转，这确保了CSP1的丰度和功能与WCC的昼夜活动紧密耦合。CSP1对自身转录的负反馈缓冲了依赖于CSP1的振荡的幅度，以对抗WCC活性的波动。CSP1主要调控与新陈代谢有关的基因。它控制麦角甾醇的合成和脂肪酸去饱和酶，从而调节细胞膜的脂质成分。
The white-collar complex (WCC), the core transcription factor of the circadian clock of Neurospora, activates morning-specific expression of the transcription repressor CSP1. Newly synthesized CSP1 exists in a transient complex with the corepressor RCM1/RCO1 and the ubiquitin ligase UBR1. CSP1 is rapidly hyperphosphorylated and degraded via UBR1 and its ubiquitin conjugase RAD6. Genes controlled by CSP1 are rhythmically expressed and peak in the evening (i.e., in antiphase to morning-specific genes directly controlled by WCC). Rhythmic expression of these second-tier genes depends crucially on phosphorylation and rapid turnover of CSP1, which ensures tight coupling of CSP1 abundance and function to the circadian activity of WCC. Negative feedback of CSP1 on its own transcription buffers the amplitude of CSP1-dependent oscillations against fluctuations of WCC activity. CSP1 predominantly regulates genes involved in metabolism. It controls ergosterol synthesis and fatty acid desaturases and thereby modulates the lipid composition of membranes.