cis Determinants of Promoter Threshold and Activation Timescale
cis Determinants of Promoter Threshold and Activation Timescale
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DOI：
10.1016/j.celrep.2015.07.035
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发表时间：
2015-08-25
期刊：
影响因子：
8.8
通讯作者：
O'Shea, Erin K.
中科院分区：
文献类型：
--
作者：
Hansen, Anders S.;O'Shea, Erin K.
虽然DNA顺式调控序列和基因表达之间的关系已被广泛研究，在稳定状态下，顺式调控序列如何影响基因诱导的动力学尚不清楚。基因诱导的动力学可以通过启动子激活时间尺度（AcTime）和幅度阈值（AmpThr）来描述。结合高通量微流体与定量延时显微镜，我们控制的芽殖酵母转录因子，Msn2的激活动力学，并揭示如何顺式调控基序在20个启动子变体的Msn2靶基因SIP18影响AcTime和AmpThr。通过调节Msn2结合位点，我们可以将AmpThr与AcTime分离，并将SIP18启动子类别从高AmpThr和慢AcTime切换为低AmpThr和快或慢AcTime。我们提出了一个模型，定量解释基因诱导动力学的基础上的Msn2结合位点的数量，TATA盒的位置，和启动子核小体组织。总之，我们阐明了TF动力学的启动子解码的顺式调控逻辑。
Although the relationship between DNA cis-regulatory sequences and gene expression has been extensively studied at steady state, how cis-regulatory sequences affect the dynamics of gene induction is not known. The dynamics of gene induction can be described by the promoter activation time-scale (AcTime) and amplitude threshold (AmpThr). Combining high-throughput microfluidics with quantitative time-lapse microscopy, we control the activation dynamics of the budding yeast transcription factor, Msn2, and reveal how cis-regulatory motifs in 20 promoter variants of the Msn2-target-gene SIP18 affect AcTime and AmpThr. By modulating Msn2 binding sites, we can decouple AmpThr from AcTime and switch the SIP18 promoter class from high AmpThr and slow AcTime to low AmpThr and either fast or slow AcTime. We present a model that quantitatively explains gene-induction dynamics on the basis of the Msn2-binding-site number, TATA box location, and promoter nucleosome organization. Overall, we elucidate the cis-regulatory logic underlying promoter decoding of TF dynamics.