A Chemical Probe for Protein Crotonylation

Area of Science:

• Biochemistry
• Epigenetics
• Chemical Biology

Background:

• Protein lysine crotonylation is an emerging post-translational modification (PTM) involved in epigenetic regulation of gene transcription.
• Existing detection methods for PTMs, such as antibody-based tools, have limitations.

Purpose of the Study:

• To develop and validate a novel chemical probe for detecting protein lysine crotonylation.
• To investigate the role of lysine crotonylation in regulating histone acetylation and gene transcription.

Main Methods:

• Synthesis of a water-soluble phosphine-based chemical probe targeting the crotonyl modification.
• Application of the chemical probe for detecting endogenous crotonylated proteins, including histones.
• Utilizing the probe to study the interaction between lysine crotonylation and histone acetyltransferase activity.

Main Results:

• The developed chemical probe effectively reacts with the crotonyl modification.
• The probe complements antibody-based methods for detecting endogenous crotonylated proteins like histones.
• Evidence of a positive feedback mechanism where lysine crotonylation activates the histone acylation activity of p300.

Conclusions:

• The novel chemical probe offers a versatile and sensitive tool for analyzing protein lysine crotonylation.
• Lysine crotonylation plays a role in regulating histone acetylation through a positive feedback loop involving p300.
• This PTM is crucial for epigenetic mechanisms governing gene transcription.