Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Proc Natl Acad Sci U S A. 2022 Mar 1;119(9). doi: 10.1073/pnas.2119187119.
Phase separation underlies the organization of the nucleus, including the biogenesis of nucleoli and the packaging of heterochromatin. Here we explore the regulation of transcription factor condensates involved in gene repression by ERK signaling in gastrulating embryos of a simple proto-vertebrate (). ERK signaling induces nuclear export of the transcriptional repressor Ets-2 repressive factor (ERF), which has been linked to various human developmental disorders. Using high-resolution imaging, we show that ERF is localized within discrete nuclear condensates that dissolve upon ERK activation. Interestingly, we observe dynamic pulses of assembly and dissociation during interphase, providing visualization of a nuclear phase separation process regulated by cell signaling. We discuss the implications of these observations for producing sharp on/off switches in gene activity and suppressing noise in cell-cell signaling events.
相分离是细胞核组织的基础,包括核仁的生物发生和异染色质的包装。在这里,我们探讨了 ERK 信号转导在简单原脊椎动物()中诱导胚层形成过程中参与基因抑制的转录因子凝聚物的调节。ERK 信号转导诱导转录抑制因子 Ets-2 抑制因子(ERF)的核输出,该因子与多种人类发育障碍有关。使用高分辨率成像,我们表明 ERF 定位于离散的核凝聚物中,这些凝聚物在 ERK 激活时溶解。有趣的是,我们观察到在有丝分裂期间组装和解离的动态脉冲,提供了受细胞信号转导调节的核相分离过程的可视化。我们讨论了这些观察结果对产生基因活性的开关和抑制细胞间信号事件中的噪声的影响。