Mitotic chromosome binding predicts transcription factor properties in interphase
Mitotic chromosome binding predicts transcription factor properties in interphase
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DOI：
10.1038/s41467-019-08417-5
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发表时间：
2019-01-30
影响因子：
16.6
通讯作者：
Suter, David M.
中科院分区：
文献类型：
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作者：
Raccaud, Mahe;Friman, Elias T.;Suter, David M.
哺乳动物转录因子 (TF) 在核迁移性和序列特异性/非特异性 DNA 结合方面存在很大差异。这些特性如何影响它们占据特定基因组位点和改变表观遗传景观的能力尚不清楚。通过荧光显微镜观察到的 TF 与有丝分裂染色体的关联很大程度上是由非特异性 DNA 相互作用介导的，并且 TF 之间存在很大差异。在这里，我们结合了 501 个 TF 有丝分裂染色体结合 (MCB) 的定量测量、光漂白后荧光恢复的 TF 迁移率测量、DNA 结合的单分子成像以及 TF 结合和染色质可及性的绘图。与有丝分裂染色体相关的转录因子在间期富含 DNA 的区室中富集，并在间期和有丝分裂中表现出较慢的移动性。值得注意的是，MCB 与相对 TF 结合率和全基因组特定位点占用率相关，但与 TF 停留时间无关。这表明转录因子的非特异性 DNA 结合特性调节其搜索效率和特定基因组位点的占用。
Mammalian transcription factors (TFs) differ broadly in their nuclear mobility and sequence-specific/non-specific DNA binding. How these properties affect their ability to occupy specific genomic sites and modify the epigenetic landscape is unclear. The association of TFs with mitotic chromosomes observed by fluorescence microscopy is largely mediated by non-specific DNA interactions and differs broadly between TFs. Here we combine quantitative measurements of mitotic chromosome binding (MCB) of 501 TFs, TF mobility measurements by fluorescence recovery after photobleaching, single molecule imaging of DNA binding, and mapping of TF binding and chromatin accessibility. TFs associating to mitotic chromosomes are enriched in DNA-rich compartments in interphase and display slower mobility in interphase and mitosis. Remarkably, MCB correlates with relative TF on-rates and genome-wide specific site occupancy, but not with TF residence times. This suggests that non-specific DNA binding properties of TFs regulate their search efficiency and occupancy of specific genomic sites.