Transcription factor CBF-1 is critical for circadian gene expression by modulating WHITE COLLAR complex recruitment to the frq locus.
Transcription factor CBF-1 is critical for circadian gene expression by modulating WHITE COLLAR complex recruitment to the frq locus.
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转录因子 CBF-1 通过调节白领复合体向 frq 基因座的募集对昼夜节律基因表达至关重要
DOI：
10.1371/journal.pgen.1007570
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发表时间：
2018-09
期刊：
影响因子：
4.5
通讯作者：
He Q
中科院分区：
文献类型：
--
作者：
Cao X;Liu X;Li H;Fan Y;Duan J;Liu Y;He Q
粗面脉孢菌生物钟基因频率(FRQ)的转录是控制昼夜节律的负反馈环路中的一个重要过程。白领1(WC-1)和白领2(WC-2)通过与其启动子结合形成WC复合体(WCC)，是FRQ转录的主要激活因子。在这里，我们证明着丝粒结合因子1(CBF-1)是通过调节FRQ转录来调节粗毛虫生物钟的关键成分。Cbf-1基因缺失导致长周期和低幅度节律，而Cbf-1过表达则使昼夜节律消失。Cbf-1的缺失导致非WC依赖的FRQ表达和WCC活性的抑制。作为WCC，CBF-1还与FRQ启动子上的C-box结合。CBF-1的过表达削弱了WCC与C-box的结合以抑制FRQ的转录。总之，我们的结果表明，适当的CBF-1水平对生物钟功能至关重要，它通过抑制WC非依赖性FRQ的表达，并通过调节WCC与FRQ启动子的结合来实现。生物钟在大约24小时的尺度上测量时间，由一个由自动调节反馈环路组成的细胞自主生物钟振荡器产生。在粗糙脉孢菌的昼夜节律振荡器中，白领复合体(WCC)激活频率(FRQ)基因的转录。FRQ抑制WCC活性，使负反馈环闭合。在这里，我们证明了转录因子CBF-1作为阻滞剂调节WCC募集到FRQ启动子的C盒。我们的数据表明，由于FRQ启动子上的WCC结合受损，CBF-1的缺失或过表达抑制了昼夜节律。由于CBF-1在真核生物中是保守的，我们的数据为控制其他生物体中生物时钟的负反馈机制提供了新的见解。
Transcription of the Neurospora crassa circadian clock gene frequency (frq) is an essential process in the negative feedback loop that controls circadian rhythms. WHITE COLLAR 1 (WC-1) and WHITE COLLAR 2 (WC-2) forms the WC complex (WCC) that is the main activator of frq transcription by binding to its promoter. Here, we show that Centromere Binding Factor 1 (CBF-1) is a critical component of the N. crassa circadian clock by regulating frq transcription. Deletion of cbf-1 resulted in long period and low amplitude rhythms, whereas overexpression of CBF-1 abolished the circadian rhythms. Loss of CBF-1 resulted in WC-independent FRQ expression and suppression of WCC activity. As WCC, CBF-1 also binds to the C-box at the frq promoter. Overexpression of CBF-1 impaired WCC binding to the C-box to suppress frq transcription. Together, our results suggest that the proper level of CBF-1 is critical for circadian clock function by suppressing WC-independent FRQ expression and by regulating WCC binding to the frq promoter. Circadian clocks, which measure time on a scale of approximately 24 hours, are generated by a cell-autonomous circadian oscillator comprised of autoregulatory feedback loops. In the Neurospora crassa circadian oscillator, WHITE COLLAR complex (WCC) actives transcription of the frequency (frq) gene. FRQ inhibits the activity of WCC to close the negative feedback loop. Here, we showed that the transcription factor CBF-1 functions as a repressor to modulate WCC recruitment to the C-box of frq promoter. Our data showed that deletion or overexpression of CBF-1 dampened circadian rhythm due to impaired WCC binding at the frq promoter. As CBF-1 is conserved in eukaryotes, our data provide novel insights into the negative feedback mechanism that controls the biological clocks in other organisms.
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影响因子：
10.5
作者：
Cheng, P;He, Q;Liu, Y
通讯作者：
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