Mapp Anna K, Ansari Aseem Z
Department of Chemistry, University of Michigan, 930 N. University Ave., Ann Arbor, Michigan 48109, USA.
ACS Chem Biol. 2007 Jan 23;2(1):62-75. doi: 10.1021/cb600463w.
Designer molecules that can be used to impose exogenous control on gene transcription, artificial transcription factors (ATFs), are highly desirable as mechanistic probes of gene regulation, as potential therapeutic agents, and as components of cell-based devices. Recently, several advances have been made in the design of ATFs that activate gene transcription (activator ATFs), including reports of small-molecule-based systems and ATFs that exhibit potent activity. However, the many open mechanistic questions about transcriptional activators, in particular, the structure and function of the transcriptional activation domain (TAD), have hindered rapid development of synthetic ATFs. A compelling need thus exists for chemical tools and insights toward a more detailed portrait of the dynamic process of gene activation.
能够用于对基因转录施加外源控制的设计分子，即人工转录因子（ATF），作为基因调控的机制性探针、潜在的治疗剂以及基于细胞的装置的组件，是非常理想的。最近，在激活基因转录的人工转录因子（激活剂ATF）的设计方面取得了一些进展，包括基于小分子的系统和表现出强效活性的人工转录因子的报道。然而，关于转录激活剂存在许多尚未解决的机制问题，特别是转录激活结构域（TAD）的结构和功能，这阻碍了合成人工转录因子的快速发展。因此，迫切需要化学工具和深入了解，以更详细地描绘基因激活的动态过程。
