Cell Death & Disease
Abstract
Although aberrant alveolar myofibroblasts (AMYFs) proliferation and differentiation are often associated with abnormal lung development and diseases, such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), epigenetic mechanisms regulating proliferation and differentiation of AMYFs remain poorly understood. Protein arginine methyltransferase 7 (PRMT7) is the only reported type III enzyme responsible for monomethylation of arginine residue on both histone and nonhistone substrates. Here we provide evidence for PRMT7’s function in regulating AMYFs proliferation and differentiation during lung alveologenesis. InPRMT7-deficient mice, we found reduced AMYFs proliferation and differentiation, abnormal elastin deposition, and failure of alveolar septum formation. We further shown that oncogene forkhead box M1 (Foxm1) is a direct target of PRMT7 and that PRMT7-catalyzed monomethylation at histone H4 arginine 3 (H4R3me1) directly associate with chromatin ofFoxm1to activate its transcription, and thereby regulate of cell cycle-related genes to inhibit AMYFs proliferation and differentiation. Overexpression ofFoxm1in isolated myofibroblasts (MYFs) significantly rescuedPRMT7-deficiency-induced cell proliferation and differentiation defects. Thus, our results reveal a novel epigenetic mechanism through which PRMT7-mediated histone arginine monomethylation activatesFoxm1transcriptional expression to regulate AMYFs proliferation and differentiation during lung alveologenesis and may represent a potential target for intervention in pulmonary diseases.
| 论文编号: | DOI:10.1038/s41419-021-04129-1 |
| 论文题目: | PRMT7 Targets of Foxm1 Controls Alveolar Myofibroblast Proliferation and Differentiation During Alveologenesis |
| 英文论文题目: | PRMT7 Targets of Foxm1 Controls Alveolar Myofibroblast Proliferation and Differentiation During Alveologenesis |
| 第一作者: | Huacheng He, Jilin Chen, Jian Zhao, Peizhun Zhang, Yulong Qiao, Huajing Wan, Jincheng Wang, Mei Mei, Shilai Bao & Qiuling Li |
| 英文第一作者: | Huacheng He, Jilin Chen, Jian Zhao, Peizhun Zhang, Yulong Qiao, Huajing Wan, Jincheng Wang, Mei Mei, Shilai Bao & Qiuling Li |
| 联系作者: | |
| 英文联系作者: | |
| 外单位作者单位: | |
| 英文外单位作者单位: | |
| 发表年度: | 2021-09-16 |
| 卷: | |
| 期: | |
| 页码: | |
| 摘要: | Although aberrant alveolar myofibroblasts (AMYFs) proliferation and differentiation are often associated with abnormal lung development and diseases, such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), epigenetic mechanisms regulating proliferation and differentiation of AMYFs remain poorly understood. Protein arginine methyltransferase 7 (PRMT7) is the only reported type III enzyme responsible for monomethylation of arginine residue on both histone and nonhistone substrates. Here we provide evidence for PRMT7’s function in regulating AMYFs proliferation and differentiation during lung alveologenesis. InPRMT7-deficient mice, we found reduced AMYFs proliferation and differentiation, abnormal elastin deposition, and failure of alveolar septum formation. We further shown that oncogene forkhead box M1 (Foxm1) is a direct target of PRMT7 and that PRMT7-catalyzed monomethylation at histone H4 arginine 3 (H4R3me1) directly associate with chromatin ofFoxm1to activate its transcription, and thereby regulate of cell cycle-related genes to inhibit AMYFs proliferation and differentiation. Overexpression ofFoxm1in isolated myofibroblasts (MYFs) significantly rescuedPRMT7-deficiency-induced cell proliferation and differentiation defects. Thus, our results reveal a novel epigenetic mechanism through which PRMT7-mediated histone arginine monomethylation activatesFoxm1transcriptional expression to regulate AMYFs proliferation and differentiation during lung alveologenesis and may represent a potential target for intervention in pulmonary diseases. |
| 英文摘要: | Although aberrant alveolar myofibroblasts (AMYFs) proliferation and differentiation are often associated with abnormal lung development and diseases, such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), epigenetic mechanisms regulating proliferation and differentiation of AMYFs remain poorly understood. Protein arginine methyltransferase 7 (PRMT7) is the only reported type III enzyme responsible for monomethylation of arginine residue on both histone and nonhistone substrates. Here we provide evidence for PRMT7’s function in regulating AMYFs proliferation and differentiation during lung alveologenesis. InPRMT7-deficient mice, we found reduced AMYFs proliferation and differentiation, abnormal elastin deposition, and failure of alveolar septum formation. We further shown that oncogene forkhead box M1 (Foxm1) is a direct target of PRMT7 and that PRMT7-catalyzed monomethylation at histone H4 arginine 3 (H4R3me1) directly associate with chromatin ofFoxm1to activate its transcription, and thereby regulate of cell cycle-related genes to inhibit AMYFs proliferation and differentiation. Overexpression ofFoxm1in isolated myofibroblasts (MYFs) significantly rescuedPRMT7-deficiency-induced cell proliferation and differentiation defects. Thus, our results reveal a novel epigenetic mechanism through which PRMT7-mediated histone arginine monomethylation activatesFoxm1transcriptional expression to regulate AMYFs proliferation and differentiation during lung alveologenesis and may represent a potential target for intervention in pulmonary diseases. |
| 刊物名称: | Cell Death & Disease |
| 英文刊物名称: | Cell Death & Disease |
| 论文全文: | |
| 英文论文全文: | |
| 全文链接: | |
| 其它备注: | Huacheng He, Jilin Chen, Jian Zhao, Peizhun Zhang, Yulong Qiao, Huajing Wan, Jincheng Wang, Mei Mei, Shilai Bao & Qiuling Li. PRMT7 Targets of Foxm1 Controls Alveolar Myofibroblast Proliferation and Differentiation During Alveologenesis. Cell Death & Disease. DOI:10.1038/s41419-021-04129-1 |
| 英文其它备注: | |
| 学科: | |
| 英文学科: | |
| 影响因子: | |
| 第一作者所在部门: | |
| 英文第一作者所在部门: | |
| 论文出处: | |
| 英文论文出处: | |
| 论文类别: | |
| 英文论文类别: | |
| 参与作者: | |
| 英文参与作者: |
