Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37593409.
- Also identified by DOI 10.1016/j.bonr.2023.101704 and PMC identifier 10430181.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Osteogenic differentiation of mesenchymal cells is controlled by epigenetic enzymes that regulate post-translational modifications of histones. Compared to acetyl or methyltransferases, the physiological functions of protein arginine methyltransferases (PRMTs) in osteoblast differentiation remain minimally understood. Therefore, we surveyed the expression and function of all nine mammalian PRMT members during osteoblast differentiation. RNA-seq gene expression profiling shows that <i>Prmt1, Prmt4/Carm1</i> and <i>Prmt5</i> represent the most prominently expressed PRMT subtypes in mouse calvarial bone and MC3T3 osteoblasts as well as human musculoskeletal tissues and mesenchymal stromal cells (MSCs). Based on effects of siRNA depletion, it appears that PRMT members have different functional effects: (i) loss of <i>Prmt1</i> stimulates and (ii) loss of <i>Prmt5</i> decreases calcium deposition of mouse MC3T3 osteoblasts, while (iii) loss of <i>Carm1</i> is inconsequential for calcium deposition. Decreased <i>Prmt5</i> suppresses expression of multiple genes involved in mineralization (e.g., <i>Alpl</i>, <i>Ibsp</i>, <i>Phospho1</i>) consistent with a positive role in osteogenesis. Depletion of <i>Prmt1, Carm1 and Prmt5</i> has intricate but modest time-dependent effects on the expression of a panel of osteoblast differentiation and proliferation markers but does not change mRNA levels for select epigenetic regulators (e.g., <i>Ezh1</i>, <i>Ezh2</i>, <i>Brd2</i> and <i>Brd4</i>). Treatment with the Class I PRMT inhibitor GSK715 enhances extracellular matrix mineralization of MC3T3 cells, while blocking formation of H3R17me2a but not H4R3me2a marks. In sum, <i>Prmt1, Carm1 and Prmt5</i> have distinct biological roles during osteoblast differentiation, and different types histone H3 and H4 arginine methylation may contribute to the chromatin landscape during osteoblast differentiation.