Division of Chromatin Networks, German Cancer Research Center (DKFZ) and Bioquant, Heidelberg, Germany.
Division of Chromatin Networks, German Cancer Research Center (DKFZ) and Bioquant, Heidelberg, Germany.
Mol Cell. 2022 May 19;82(10):1878-1893.e10. doi: 10.1016/j.molcel.2022.04.017. Epub 2022 May 9.
Transcription factors (TFs) consist of a DNA-binding domain and an activation domain (AD) that are frequently considered to be independent and exchangeable modules. However, recent studies report that the physicochemical properties of the AD can control TF assembly at chromatin by driving phase separation into transcriptional condensates. Here, we dissected transcription activation by comparing different synthetic TFs at a reporter gene array with real-time single-cell fluorescence microscopy. In these experiments, binding site occupancy, residence time, and coactivator recruitment in relation to multivalent TF interactions were compared. While phase separation propensity and activation strength of the AD were linked, the actual formation of liquid-like TF droplets had a neutral or inhibitory effect on transcription activation. We conclude that multivalent AD-mediated interactions enhance the transcription activation capacity of a TF by increasing its residence time in the chromatin-bound state and facilitating the recruitment of coactivators independent of phase separation.
转录因子 (TFs) 由 DNA 结合域和激活域 (AD) 组成，通常被认为是独立且可互换的模块。然而，最近的研究报告称，AD 的物理化学性质可以通过驱动相分离到转录凝聚物中来控制染色质上的 TF 组装。在这里，我们通过在报告基因阵列上用实时单细胞荧光显微镜比较不同的合成 TF 来剖析转录激活。在这些实验中，比较了结合位点占有率、停留时间以及与多价 TF 相互作用有关的共激活因子募集。虽然 AD 的相分离倾向和激活强度相关联，但液态样 TF 液滴的实际形成对转录激活具有中性或抑制作用。我们的结论是，多价 AD 介导的相互作用通过增加 TF 在染色质结合状态下的停留时间并促进共激活因子的募集，从而增强 TF 的转录激活能力，而与相分离无关。
