Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 Rue René Descartes, 67084 Strasbourg, France.
Nucleic Acids Res. 2014 Feb;42(4):2171-84. doi: 10.1093/nar/gkt1136. Epub 2013 Nov 14.
A transcriptional feedback loop is the simplest and most direct means for a transcription factor to provide an increased stability of gene expression. In this work performed in human cells, we reveal a new negative auto-regulatory mechanism involving an alternative transcription start site (TSS) usage. Using the activating transcription factor ZNF143 as a model, we show that the ZNF143 low-affinity binding sites, located downstream of its canonical TSS, play the role of protein sensors to induce the up- or down-regulation of ZNF143 gene expression. We uncovered that the TSS switch that mediates this regulation implies the differential expression of two transcripts with an opposite protein production ability due to their different 5' untranslated regions. Moreover, our analysis of the ENCODE data suggests that this mechanism could be used by other transcription factors to rapidly respond to their own aberrant expression level.
转录反馈回路是转录因子提供基因表达稳定性增加的最简单和最直接的手段。在这项在人类细胞中进行的工作中，我们揭示了一种涉及替代转录起始位点（TSS）使用的新的负自动调节机制。使用激活转录因子 ZNF143 作为模型，我们表明，位于其典型 TSS 下游的 ZNF143 低亲和力结合位点充当蛋白传感器，以诱导 ZNF143 基因表达的上调或下调。我们发现，介导这种调节的 TSS 切换暗示了两种具有相反蛋白产生能力的转录本的差异表达，这是由于它们不同的 5'非翻译区。此外，我们对 ENCODE 数据的分析表明，这种机制可能被其他转录因子用来快速响应它们自身异常的表达水平。
