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Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells
Published on: January 5, 2024
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MYC phase separation selectively modulates the transcriptome
Junjiao Yang1,2, Chan-I Chung1,2, Jessica Koach3
1Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Nature Structural & Molecular Biology
|May 29, 2024
Summary
MYCN (a transcription factor) can form condensates that regulate gene expression in cancer. While phase separation impacts key oncogenes and cell proliferation, most MYCN-regulated genes do not require this process for activation.
Area of Science:
- Molecular Biology
- Cancer Biology
- Biochemistry
Background:
- Dysregulation of MYC transcription factors (TFs), including MYCN, is common in human cancers.
- MYCN amplification in high-risk neuroblastoma leads to overexpression, driving cell proliferation.
- The role of MYCN's phase separation in transcriptional regulation is not fully understood.
Purpose of the Study:
- To investigate the phase behavior of MYCN and its role in transcriptional regulation.
- To determine if MYCN forms phase-separated condensates with transcriptional hallmarks.
- To assess the impact of MYCN phase separation on gene activation and cell proliferation.
Main Methods:
- Characterization of MYCN's phase behavior.
- Utilizing a chemogenetic tool to compare phase-separated and non-phase-separated conditions at equivalent MYCN levels.
- Analysis of gene expression changes and cell proliferation rates.
Main Results:
- MYCN forms dynamic condensates with transcriptional hallmarks.
- Phase separation significantly impacts a small subset (<3%) of MYCN-regulated genes, including oncogenes and tumor suppressors.
- MYCN phase separation enhances cell proliferation.
- The majority (>97%) of MYCN-regulated genes are activated by soluble MYCN complexes.
Conclusions:
- MYCN can form phase-separated condensates that contribute to cancer progression.
- While phase separation influences specific key genes, soluble MYCN complexes are sufficient for most transcriptional activation.
- Understanding MYCN's phase separation offers potential therapeutic targets for MYCN-driven cancers.
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