Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, China.
Nat Commun. 2021 May 25;12(1):3145. doi: 10.1038/s41467-021-23425-0.
Recent single-cell studies have revealed that yeast stress response involves transcription factors that are activated in pulses. However, it remains unclear whether and how these dynamic transcription factors temporally interact to regulate stress survival. Here we show that budding yeast cells can exploit the temporal relationship between paralogous general stress regulators, Msn2 and Msn4, during stress response. We find that individual pulses of Msn2 and Msn4 are largely redundant, and cells can enhance the expression of their shared targets by increasing their temporal divergence. Thus, functional redundancy between these two paralogs is modulated in a dynamic manner to confer fitness advantages for yeast cells, which might feed back to promote the preservation of their redundancy. This evolutionary implication is supported by evidence from Msn2/Msn4 orthologs and analyses of other transcription factor paralogs. Together, we show a cell fate control mechanism through temporal redundancy modulation in yeast, which may represent an evolutionarily important strategy for maintaining functional redundancy between gene duplicates.
最近的单细胞研究表明，酵母应激反应涉及在脉冲中被激活的转录因子。然而，目前尚不清楚这些动态转录因子是否以及如何在时间上相互作用来调节应激生存。在这里，我们表明，出芽酵母细胞可以在应激反应期间利用同源一般应激调节剂 Msn2 和 Msn4 之间的时间关系。我们发现，Msn2 和 Msn4 的单个脉冲在很大程度上是冗余的，并且细胞可以通过增加它们的时间发散来增强它们共享靶标的表达。因此，这两个同源物之间的功能冗余以动态方式进行调节，为酵母细胞赋予了适应优势，这可能反馈促进它们冗余的保存。这一进化意义得到了 Msn2/Msn4 同源物的证据和其他转录因子同源物的分析的支持。总之，我们在酵母中展示了一种通过时间冗余调节来控制细胞命运的机制，这可能代表了在基因重复之间维持功能冗余的一种重要的进化策略。
