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Histone probes for reader and eraser investigations
Jinyu Yang1, Mingxuan Wu1,2,3
1Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, Department of Chemistry, School of Science, Westlake University Hangzhou 310030 Zhejiang Province China wumingxuan@westlake.edu.cn.
Chemical Science
|October 30, 2025
Summary
Chemical probes are vital for studying histone modifications, which regulate gene expression. This review covers affinity, photoreactive, and activity-based probes for identifying histone-modifying enzymes and proteins.
Area of Science:
- Chemical Biology
- Epigenetics
- Molecular Biology
Background:
- Histone modifications regulate gene transcription and epigenetic inheritance.
- Writers, erasers, and readers are key enzymes and proteins involved in histone mark regulation.
- Investigating these proteins is crucial for understanding histone modification roles.
Purpose of the Study:
- To review the development of chemical probes for studying histone modification readers and erasers.
- To highlight the advantages and limitations of different probe types.
Main Methods:
- Discussion of affinity-based probes for protein enrichment.
- Introduction of photoreactive probes for covalent crosslinking.
- Summary of activity-based probes targeting enzyme active sites.
Main Results:
- Affinity probes are limited for low-abundance or transient proteins.
- Photoreactive probes enable UV-induced crosslinking of proteins of interest.
- Activity-based probes offer selective binding and crosslinking of readers and erasers.
Conclusions:
- Chemical probes are essential tools for investigating histone modification pathways.
- Covalent crosslinking probes overcome limitations of affinity-based methods.
- Future directions include addressing challenges and exploring new probe designs.
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