The Arginine Methyltransferase PRMT6 Cooperates with Polycomb Proteins in Regulating HOXA Gene Expression

Area of Science:

• Epigenetics
• Gene Regulation
• Molecular Biology

Background:

• Protein arginine methyltransferase 6 (PRMT6) catalyzes H3R2me2a, inhibiting H3K4me3 deposition by blocking the MLL1 complex.
• H3R2me2a genomic occurrence coincides with H3K27me3, a repressive mark generated by Polycomb repressive complex 2 (PRC2).

Purpose of the Study:

• Investigate the crosstalk between PRMT6- and PRC-mediated repression during neuronal differentiation.
• Elucidate PRMT6's role in gene repression through cooperation with Polycomb proteins.

Main Methods:

• Utilized a cellular model of neuronal differentiation.
• Examined binding of PRMT6, PRC2, and PRC1 subunits to rostral HOXA gene regulatory regions.
• Assessed the impact of PRMT6 depletion on histone mark occupancy (H3K4me3, H3K27me3) and Polycomb occupancy (PRC1, PRC2).

Main Results:

• PRMT6, PRC1, and PRC2 subunits bind to the same regulatory regions of rostral HOXA genes, controlling their differentiation-associated activation.
• PRMT6 interacts with PRC1 and PRC2 subunits.
• PRMT6 depletion leads to reduced PRC1/PRC2 and H3K27me3 occupancy, alongside increased H3K4me3 levels at target genes.

Conclusions:

• PRMT6 cooperates with Polycomb proteins (PRC1 and PRC2) to repress gene expression.
• This cooperation represents a novel mechanism contributing to PRMT6-mediated gene silencing.
• The findings highlight a new layer of epigenetic regulation involving PRMT6 and Polycomb complexes in controlling gene expression during differentiation.