ERK signaling dissolves ERF repression condensates in living embryos
Claire J Weaver1,2, Aleena L Patel1,2, Stanislav Y Shvartsman1,2,3
1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.
Summary
Cell signaling regulates gene repression by controlling the assembly and disassembly of transcription factor condensates. This dynamic nuclear phase separation process, visualized in Ciona embryos, impacts gene activity switches.
Area of Science:
- Cell biology
- Developmental biology
- Molecular signaling
Background:
- Nuclear organization relies on phase separation for processes like nucleoli biogenesis and heterochromatin packaging.
- Dysregulation of transcription factors and signaling pathways can lead to developmental disorders.
Purpose of the Study:
- To investigate the regulation of transcription factor condensates by ERK signaling during gastrulation in Ciona embryos.
- To visualize the dynamic behavior of these condensates and their relationship to gene repression.
Main Methods:
- High-resolution live imaging of nuclear condensates in Ciona embryos.
- Analysis of Ets-2 repressive factor (ERF) localization and dynamics.
- Correlation of ERK signaling activation with condensate dissolution.
Main Results:
- The transcriptional repressor ERF localizes to discrete nuclear condensates.
- ERK signaling activation triggers the dissolution of these ERF condensates.
- Dynamic pulses of condensate assembly and dissociation were observed during interphase, illustrating regulated nuclear phase separation.
Conclusions:
- ERK signaling dynamically regulates nuclear phase separation of transcription factors involved in gene repression.
- This mechanism provides sharp on/off switches for gene activity and reduces noise in cell signaling.
- Understanding this process has implications for human developmental disorders linked to ERF and signaling pathways.
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