Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation
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 mi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Bone Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352187223000529 |
| _version_ | 1797398568930115584 |
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| author | Parisa Dashti Eric A. Lewallen Jonathan A.R. Gordon Martin A. Montecino Johannes P.T.M. van Leeuwen Gary S. Stein Bram C.J. van der Eerden James R. Davie Andre J. van Wijnen |
| author_facet | Parisa Dashti Eric A. Lewallen Jonathan A.R. Gordon Martin A. Montecino Johannes P.T.M. van Leeuwen Gary S. Stein Bram C.J. van der Eerden James R. Davie Andre J. van Wijnen |
| author_sort | Parisa Dashti |
| collection | DOAJ |
| description | 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 Prmt1, Prmt4/Carm1 and Prmt5 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 Prmt1 stimulates and (ii) loss of Prmt5 decreases calcium deposition of mouse MC3T3 osteoblasts, while (iii) loss of Carm1 is inconsequential for calcium deposition. Decreased Prmt5 suppresses expression of multiple genes involved in mineralization (e.g., Alpl, Ibsp, Phospho1) consistent with a positive role in osteogenesis. Depletion of Prmt1, Carm1 and Prmt5 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., Ezh1, Ezh2, Brd2 and Brd4). 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, Prmt1, Carm1 and Prmt5 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. |
| first_indexed | 2024-03-09T01:27:22Z |
| format | Article |
| id | doaj.art-782923f9b7f54150befe4cda6e4e94a7 |
| institution | Directory Open Access Journal |
| issn | 2352-1872 |
| language | English |
| last_indexed | 2024-03-09T01:27:22Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Bone Reports |
| spelling | doaj.art-782923f9b7f54150befe4cda6e4e94a72023-12-10T06:16:18ZengElsevierBone Reports2352-18722023-12-0119101704Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiationParisa Dashti0Eric A. Lewallen1Jonathan A.R. Gordon2Martin A. Montecino3Johannes P.T.M. van Leeuwen4Gary S. Stein5Bram C.J. van der Eerden6James R. Davie7Andre J. van Wijnen8Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USADepartment of Biological Sciences, Hampton University, Hampton, VA, USADepartment of Biochemistry, University of Vermont, Burlington, VT, USAInstitute of Biomedical Sciences, Faculty of Medicine, Universidad Andres Bello, Santiago, ChileDepartment of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Biochemistry, University of Vermont, Burlington, VT, USADepartment of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands; Corresponding author.Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada; CancerCare Manitoba Research Institute, CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada; Correspondence to: J. R. Davie, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Biochemistry, University of Vermont, Burlington, VT, USA; Correspondence to: A. J. van Wijnen, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands.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 Prmt1, Prmt4/Carm1 and Prmt5 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 Prmt1 stimulates and (ii) loss of Prmt5 decreases calcium deposition of mouse MC3T3 osteoblasts, while (iii) loss of Carm1 is inconsequential for calcium deposition. Decreased Prmt5 suppresses expression of multiple genes involved in mineralization (e.g., Alpl, Ibsp, Phospho1) consistent with a positive role in osteogenesis. Depletion of Prmt1, Carm1 and Prmt5 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., Ezh1, Ezh2, Brd2 and Brd4). 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, Prmt1, Carm1 and Prmt5 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.http://www.sciencedirect.com/science/article/pii/S2352187223000529BoneOsteoblastOsteogenesisEpigeneticsChromatinHistone |
| spellingShingle | Parisa Dashti Eric A. Lewallen Jonathan A.R. Gordon Martin A. Montecino Johannes P.T.M. van Leeuwen Gary S. Stein Bram C.J. van der Eerden James R. Davie Andre J. van Wijnen Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation Bone Reports Bone Osteoblast Osteogenesis Epigenetics Chromatin Histone |
| title | Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation |
| title_full | Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation |
| title_fullStr | Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation |
| title_full_unstemmed | Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation |
| title_short | Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation |
| title_sort | protein arginine methyltransferases prmt1 prmt4 carm1 and prmt5 have distinct functions in control of osteoblast differentiation |
| topic | Bone Osteoblast Osteogenesis Epigenetics Chromatin Histone |
| url | http://www.sciencedirect.com/science/article/pii/S2352187223000529 |
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