Optogenetic perturbations, live imaging, and time-resolved ChIP-seq assays in Drosophila embryos were used to dissect the ERK-dependent control of the HMG-box repressor Capicua (Cic), which plays critical roles in development and is deregulated in human spinocerebellar ataxia and cancers. We established that Cic target genes are activated before significant downregulation of nuclear localization of Cic and demonstrated that their activation is preceded by fast dissociation of Cic from the regulatory DNA. We discovered that both Cic-DNA binding and repression are rapidly reinstated in the absence of ERK activation, revealing that inductive signaling must be sufficiently sustained to ensure robust transcriptional response. Our work provides a quantitative framework for the mechanistic analysis of dynamics and control of transcriptional repression in development.

中文翻译：

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Capicua信号依赖转录抑制的快速动力学。

果蝇胚胎中的光遗传学扰动，实时成像和时间分辨的ChIP-seq分析用于解剖HMG框阻遏物Capicua（Cic）的ERK依赖性控制，后者在发育中起着关键作用，并在人类脊髓小脑共济失调中失控和癌症。我们确定Cic目标基因在Cic的核定位显着下调之前已被激活，并证明了它们的激活是Cic与调控DNA的快速解离所致。我们发现，在没有ERK激活的情况下，Cic-DNA的结合和阻抑作用都可以迅速恢复，这表明诱导信号必须充分维持以确保强大的转录反应。