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Updated: Jul 10, 2026
11:34
Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
Opposing function of AEBP2 isoforms fine-tune PRC2 catalytic activity.
Yingying Li1,2, Cheolan Kwon1,3, Hanbyeol Kim1,2
1Department of Pharmacology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
Nucleic Acids Research
|July 9, 2026
Summary
The long isoform of AEBP2 inhibits Polycomb repressive complex 2 (PRC2) activity via unique DE-motifs, impacting H3K27 methylation and cellular differentiation.
Area of Science:
- Epigenetics
- Developmental Biology
- Molecular Biology
Background:
- Polycomb repressive complex 2 (PRC2) is crucial for gene silencing and maintaining cellular identity via H3K27me3 histone modification.
- Accessory proteins modulate PRC2 function, with AEBP2 having known short and unclear long isoforms.
Purpose of the Study:
- To investigate the function of the long AEBP2 isoform and its role in regulating PRC2 activity.
- To elucidate the mechanism by which the long AEBP2 isoform controls PRC2 during mouse development.
Main Methods:
- Analysis of conserved DE-motifs in the N-terminal region of the long AEBP2 isoform.
- Biochemical assays to assess PRC2 catalytic activity (H3K27 methylation and EZH2 automethylation).
- Re-expression studies in triple-knockout mouse embryonic stem cells (Mtf2/Jarid2/Aebp2).
Main Results:
- The long AEBP2 isoform's N-terminal DE-motifs were found to inhibit PRC2 activity, including H3K27 methylation and EZH2 automethylation.
- Re-expression of the long AEBP2 isoform in knockout cells did not restore H3K27me3 levels.
- Defective cellular differentiation was observed upon re-expression of the long AEBP2 isoform in knockout cells.
Conclusions:
- AEBP2 exhibits isoform-specific regulation of PRC2 activity through its N-terminal DE-motifs.
- The long AEBP2 isoform plays a critical role in PRC2-mediated gene repression and proper cellular differentiation during development.
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