Light-induced changes in the suprachiasmatic nucleus transcriptome regulated by the ERK/MAPK pathway.

Light-induced changes in the suprachiasmatic nucleus transcriptome regulated by the ERK/MAPK pathway.
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DOI:
10.1371/journal.pone.0249430
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Obrietan K
Obrietan K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alzate-Correa D;Aten S;Campbell MJ;Hoyt KR;Obrietan K

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在视交叉上核(SCN)内的哺乳动物主昼夜节律起搏器通过振荡器对光的响应中的复杂的时钟门控节律维持对24小时光/暗周期的紧密夹带。在这个光夹带过程中的一个中心事件似乎是通过ERK/MAPK途径快速诱导基因表达。在这里,我们使用基于RNA阵列的分析与药理学破坏方法相结合,以检查ERK/MAPK信号转导对光诱发的基因表达的贡献。在昼夜节律的夜晚,但不是在昼夜节律的白天,瞬时光刺激,触发了基因表达的显着变化,与深夜光主要导致基因表达增加和基因下调。功能分析表明,光调控基因参与多种生理过程,包括DNA转录、RNA翻译、mRNA加工、突触可塑性和昼夜节律定时。MAPK信号传导的破坏导致在夜间早期(32/52个基因)和深夜(190/191个基因)期间光诱发的基因调控显著减少;此外,发现MAPK信号传导在昼夜节律周期中门控基因表达。总之,这些实验揭示了潜在的重要见解,以转录为基础的机制,ERK/MAPK途径调节昼夜节律时钟的时间和光诱发的时钟夹带。
The mammalian master circadian pacemaker within the suprachiasmatic nucleus (SCN) maintains tight entrainment to the 24 hr light/dark cycle via a sophisticated clock-gated rhythm in the responsiveness of the oscillator to light. A central event in this light entrainment process appears to be the rapid induction of gene expression via the ERK/MAPK pathway. Here, we used RNA array-based profiling in combination with pharmacological disruption methods to examine the contribution of ERK/MAPK signaling to light-evoked gene expression. Transient photic stimulation during the circadian night, but not during the circadian day, triggered marked changes in gene expression, with early-night light predominately leading to increased gene expression and late-night light predominately leading to gene downregulation. Functional analysis revealed that light-regulated genes are involved in a diversity of physiological processes, including DNA transcription, RNA translation, mRNA processing, synaptic plasticity and circadian timing. The disruption of MAPK signaling led to a marked reduction in light-evoked gene regulation during the early night (32/52 genes) and late night (190/191 genes); further, MAPK signaling was found to gate gene expression across the circadian cycle. Together, these experiments reveal potentially important insights into the transcriptional-based mechanisms by which the ERK/MAPK pathway regulates circadian clock timing and light-evoked clock entrainment.
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影响因子: 4.7
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