University Department of Zoology, Vinoba Bhave University, Hazaribag 825 301, India.
J Genet. 2021;100.
Transcription factors play very important role in cell fate determination. There are many cell specific transcription factors which when expressed ectopically may lead to cell fate conversion or transdifferentiation. Many of these transcription factors function differently based on their levels and stoichiometry. Many different types of differentiated cells have been generated from other differentiated cell types by expressing different levels and stoichiometry of reprogramming factors. Many methodologies have been developed for efficient cell fate conversion by regulating the levels and stoichiometry of transcription factors in a particular cocktail that have therapeutic values. An approach called phenotypic activation which involves overexpression of putative transcription factors has been developed as a tool to discover new transcription factors and their targets. Transcription factor overexpression may also have toxic effects where nonspecific electrostatic interactions and 'squelching' may lead to inhibition of many genes. Altered levels of transcription factors may have disastrous consequences like cancer. Recent developments like designing of artificial transcription factors, nanotechnology-based transcriptional tools and CRISPR-based transcription modules with capabilities of precise regulation of gene expression patterns hold huge potentials in the field of transcriptional therapeutics.
转录因子在细胞命运决定中起着非常重要的作用。有许多细胞特异性转录因子,当异位表达时,可能导致细胞命运转换或转分化。许多转录因子的功能因其水平和化学计量比而异。通过表达不同水平和化学计量比的重编程因子,已经从其他分化细胞类型中产生了许多不同类型的分化细胞。已经开发出许多方法来通过调节特定鸡尾酒中转录因子的水平和化学计量比来有效进行细胞命运转换,这些方法具有治疗价值。一种称为表型激活的方法,涉及过表达假定的转录因子,已被开发为发现新的转录因子及其靶标的工具。转录因子的过表达也可能产生毒性作用,其中非特异性静电相互作用和“抑制”可能导致许多基因的抑制。转录因子水平的改变可能会产生灾难性的后果,如癌症。最近的发展,如人工转录因子的设计、基于纳米技术的转录工具和基于 CRISPR 的转录模块,具有精确调节基因表达模式的能力,在转录治疗领域具有巨大的潜力。