Zheng Chaogu, Chalfie Martin
Department of Biological Sciences, Columbia University, New York, USA.
Department of Biological Sciences, Columbia University, New York, USA.
Curr Top Dev Biol. 2016;116:167-80. doi: 10.1016/bs.ctdb.2015.11.011. Epub 2016 Jan 23.
Transcription factors control neuronal differentiation by acting as "terminal selectors" that determine the specific cell fates of different types of neurons. The specification of cell fate, however, requires high fidelity, which relies on stable and robust expression of the terminal selectors. Our recent studies in C. elegans suggest that a second set of transcription factors function as reinforcing or protecting factors to stabilize the expression and activity of terminal selectors. Some serve as "guarantors" to ensure the activation and continuous expression of the selectors by reducing stochastic fluctuations in gene expression; others safeguard the protein function of selectors by repressing inhibitors that would block their activity. These transcription factors, unlike the terminal selectors, do not induce specification but secure neuronal cell fate and provide reliability in differentiation.
转录因子通过作为“终末选择因子”来控制神经元分化,这些“终末选择因子”决定了不同类型神经元的特定细胞命运。然而,细胞命运的特化需要高保真度,这依赖于终末选择因子的稳定且强劲的表达。我们最近在秀丽隐杆线虫中的研究表明,另一组转录因子作为增强或保护因子,来稳定终末选择因子的表达和活性。一些转录因子充当“担保人”,通过减少基因表达中的随机波动来确保选择因子的激活和持续表达;另一些则通过抑制会阻断其活性的抑制剂来保护选择因子的蛋白质功能。与终末选择因子不同,这些转录因子不会诱导特化,而是确保神经元细胞命运并为分化提供可靠性。