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Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells
Published on: August 7, 2021
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PRMT1-mediated methylation regulates MLL2 stability and gene expression
Dongju An1, Jihyun Kim1, Byul Moon2
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea.
Nucleic Acids Research
|December 19, 2024
Summary
Protein methyltransferases MLL2 (KMT2B) and PRMT1 interact to regulate gene expression. PRMT1 methylation stabilizes MLL2, impacting cell functions like migration and invasion.
Area of Science:
- Molecular Biology
- Epigenetics
- Gene Regulation
Background:
- Eukaryotic transcription is precisely regulated by the interplay of multiple transcription factors.
- Protein methyltransferases play crucial roles in modulating protein function and stability.
Purpose of the Study:
- To investigate the interaction and collective function of MLL2 (KMT2B) and PRMT1 in gene expression regulation.
- To elucidate the mechanism by which PRMT1 affects MLL2 stability and activity.
Main Methods:
- Co-immunoprecipitation to confirm protein-protein interaction.
- Site-directed mutagenesis to identify methylation sites on MLL2.
- Western blotting to assess protein ubiquitylation and stability.
- Chromosomal reporter gene assays to measure transcriptional activity.
- RNA-sequencing (RNA-seq) to analyze gene expression changes.
- Gene depletion studies (e.g., siRNA or shRNA) to assess functional consequences.
Main Results:
- MLL2 (KMT2B) and PRMT1 directly interact, with PRMT1 binding to the intrinsically disordered N-terminal region of MLL2.
- PRMT1 methylates arginine residues in MLL2's RGG/RG motifs, decreasing MLL2 poly-ubiquitylation and enhancing its stability.
- PRMT1-mediated MLL2 methylation cooperatively stimulates gene expression in a methylation-dependent manner.
- Jointly regulated genes are involved in cell membrane and extracellular matrix functions.
- Depletion of either MLL2 or PRMT1 impairs cell migration and invasion.
Conclusions:
- PRMT1-mediated methylation is a key mechanism for regulating MLL2 protein stability.
- The MLL2-PRMT1 complex collectively regulates gene expression, impacting cellular functions critical for migration and invasion.
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