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Updated: Nov 11, 2025
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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
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The deubiquitinase Usp9x regulates PRC2-mediated chromatin reprogramming during mouse development
Trisha A Macrae1,2,3,4, Miguel Ramalho-Santos5,6,7,8
1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Nature Communications
|March 26, 2021
Summary
The deubiquitinase Usp9x stabilizes Polycomb Repressive Complex 2 (PRC2), controlling H3K27me3 levels during embryonic stem cell self-renewal and lineage commitment. This Usp9x-PRC2 axis is crucial for early mammalian development and may play roles in disease.
Area of Science:
- Developmental Biology
- Epigenetics
- Cell Biology
Background:
- Pluripotent cells require chromatin remodeling for lineage commitment post-implantation.
- Polycomb Repressive Complex 2 (PRC2) deposits H3K27me3, a mark that shifts during embryonic development.
- Mechanisms regulating H3K27me3 redistribution remain largely unknown.
Purpose of the Study:
- To investigate the post-translational regulation of PRC2 and H3K27me3.
- To elucidate the role of Usp9x in embryonic stem cell self-renewal and chromatin modification.
- To understand the developmental consequences of Usp9x-PRC2 axis disruption.
Main Methods:
- Utilized an auxin-inducible degron system in mouse embryonic stem cells.
- Investigated protein-protein interactions between Usp9x and PRC2.
- Analyzed H3K27me3 distribution and gene expression in Usp9x-deficient cells and embryos.
Main Results:
- Usp9x is essential for mouse embryonic stem cell self-renewal and maintains high PRC2 levels.
- Usp9x interacts with, deubiquitinates, and stabilizes PRC2.
- Usp9x depletion in embryos leads to derepression of developmental genes and morphological defects.
Conclusions:
- A novel Usp9x-PRC2 regulatory axis controls H3K27me3 dynamics during early mammalian development.
- This axis is critical for peri-implantation development and stem cell fate.
- Usp9x's role in PRC2 regulation suggests implications in stem cell transitions and diseases like cancer and neurological disorders.
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