Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation.
Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation.
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Hox 蛋白充当转录保证子以确保终末分化。
DOI：
10.1016/j.celrep.2015.10.044
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发表时间：
2015
期刊：
影响因子：
8.8
通讯作者：
Chalfie,Martin
中科院分区：
文献类型：
--
作者：
Zheng,Chaogu;Jin,FelixQiaochu;Chalfie,Martin
细胞分化通常以高保真度发生，但许多转录因子的表达是可变的。使用 C 中的触摸感受器神经元 (TRN)。 在线虫中，我们发现 Hox 蛋白 CEH-13/lab 和 EGL-5/Abd-B 通过分别促进前 TRN 和后 TRN 中共同 TRN 命运决定因素 mec-3 的激活来克服这种变异性。 CEH-13 和 EGL-5 使用相同的 Hox/Pbx 结合位点增加了 POU-同源域转录因子 UNC-86 激活 mec-3 转录的可能性。 ceh-13andegl-5 的突变导致各自 TRN 中 TRN 命运的不完全（~40%）损失，这与显示 mec-3 转录的两种不同模式（全部或无）的定量 mRNA 测量相关。因此，Hox蛋白充当转录“保证者”，以确保终末神经元分化过程中可靠且稳健的基因表达。保证子本身并不激活基因表达，而是促进受其他转录因子调节的靶基因的完全激活。
Cell differentiation usually occurs with high fidelity, but the expression of many transcription factors is variable. Using the touch receptor neurons (TRNs) inC. elegans, we found that the Hox proteins CEH-13/lab and EGL-5/Abd-B overcome this variability by facilitating the activation of the common TRN fate determinantmec-3in the anterior and posterior TRNs, respectively. CEH-13 and EGL-5 increase the probability ofmec-3transcriptional activation by the POU-homeodomain transcription factor UNC-86 using the same Hox/Pbx binding site. Mutation ofceh-13andegl-5resulted in an incomplete (∼40%) loss of the TRN fate in respective TRNs, which correlates with quantitative mRNA measurements showing two distinct modes (all or none) ofmec-3transcription. Therefore, Hox proteins act as transcriptional "guarantors" in order to ensure reliable and robust gene expression during terminal neuronal differentiation. Guarantors do not activate gene expression by themselves but promote full activation of target genes regulated by other transcription factors.