Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
Interdisciplinary Doctoral Programme in Biomedicine, University of Ljubljana, Kongresni trg 12, SI-1000 Ljubljana, Slovenia.
Nucleic Acids Res. 2022 Jun 24;50(11):6562-6574. doi: 10.1093/nar/gkac454.
DNA transcription is regulated by a range of diverse mechanisms and primarily by transcription factors that recruit the RNA polymerase complex to the promoter region on the DNA. Protein binding to DNA at nearby or distant sites can synergistically affect this process in a variety of ways, but mainly through direct interactions between DNA-binding proteins. Here we show that a Transcription Activator-Like Effector (TALE), which lacks an activation domain, can enhance transcription in mammalian cells when it binds in the vicinity of and without direct interaction with several different dimeric or monomeric transcription factors. This effect was observed for several TALEs regardless of the recognition sequences and their DNA-bound orientation. TALEs can exert an effect over the distance of tens of nucleotides and it also potentiated KRAB-mediated repression. The augmentation of transcriptional regulation of another transcription factor is characteristic of TALEs, as it was not observed for dCas9/gRNA, zinc finger, or Gal4 DNA-binding domains. We propose that this mechanism involves an allosteric effect exerted on DNA structure or dynamics. This mechanism could be used to modulate transcription but may also play a role in the natural context of TALEs.
DNA 转录受多种不同机制的调节，主要由转录因子调节，转录因子将 RNA 聚合酶复合物募集到 DNA 的启动子区域。蛋白质在附近或远处与 DNA 的结合可以通过多种方式协同影响这一过程，但主要是通过 DNA 结合蛋白之间的直接相互作用。在这里，我们表明，一种缺乏激活结构域的转录激活子样效应因子（TALE），当它在附近结合但不与几个不同的二聚体或单体转录因子直接相互作用时，可以增强哺乳动物细胞中的转录。这种效应在几种 TALEs 中都观察到，无论识别序列及其 DNA 结合方向如何。TALEs 可以在数十个核苷酸的距离上发挥作用，并且还增强了 KRAB 介导的抑制。另一种转录因子的转录调控增强是 TALEs 的特征，因为 dCas9/gRNA、锌指或 Gal4 DNA 结合结构域没有观察到这种现象。我们提出，这种机制涉及对 DNA 结构或动力学的变构效应。这种机制可用于调节转录，但也可能在 TALEs 的自然环境中发挥作用。
