CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]

Publication Date:
2018-11-10
Publisher:
The American Society for Biochemistry and Molecular Biology (ASBMB)
Print ISSN:
0021-9258
Electronic ISSN:
1083-351X
Topics:
Biology
Chemistry and Pharmacology
Published by:
http://www.asbmb.org/
_version_ 1836399084943966208
autor Min Nie, Yadong Wang, Chan Guo, Xinyu Li, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Chi Ma, Ming Liu, Panxue Wang, Ruoyun Wang, Renxiang Tan, Ming Fang, Bing Chen, Yinghong He, David C. S. Huang, Junyi Ju, Quan Zhao
beschreibung Protein arginine methyltransferase 5 (PRMT5) is a member of the arginine methyltransferase protein family that critically mediates the symmetric dimethylation of Arg-3 at histone H4 (H4R3me2s) and is involved in many key cellular processes, including hematopoiesis. However, the post-translational modifications (PTMs) of PRMT5 that may affect its biological functions remain less well-understood. In this study, using MS analyses, we found that PRMT5 itself is methylated in human erythroleukemia Lys-562 cells. Biochemical assays revealed that coactivator-associated arginine methyltransferase 1 (CARM1) interacts directly with and methylates PRMT5 at Arg-505 both in vivo and in vitro. Substitutions at Arg-505 significantly reduced PRMT5's methyltransferase activity, decreased H4R3me2s enrichment at the γ-globin gene promoter, and increased the expression of the γ-globin gene in Lys-562 cells. Moreover, CARM1 knockdown consistently reduced PRMT5 activity and activated γ-globin gene expression. Importantly, we show that CARM1-mediated methylation of PRMT5 is essential for the intracellular homodimerization of PRMT5 to its active form. These results thus reveal a critical PTM of PRMT5 that represses human γ-globin gene expression. We conclude that CARM1-mediated asymmetric methylation of PRMT5 is critical for its dimerization and methyltransferase activity leading to the repression of γ-globin expression. Given PRMT5's crucial role in diverse cellular processes, these findings may inform strategies for manipulating its methyltransferase activity for managing hemoglobinopathy or cancer.
citation_standardnr 6355791
datenlieferant ipn_articles
feed_id 43
feed_publisher The American Society for Biochemistry and Molecular Biology (ASBMB)
feed_publisher_url http://www.asbmb.org/
insertion_date 2018-11-10
journaleissn 1083-351X
journalissn 0021-9258
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Society for Biochemistry and Molecular Biology (ASBMB)
quelle Journal of Biological Chemistry
relation http://feedproxy.google.com/~r/jbc/SUcv/~3/_rx2nGBCX3E/17454.short
search_space articles
shingle_author_1 Min Nie, Yadong Wang, Chan Guo, Xinyu Li, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Chi Ma, Ming Liu, Panxue Wang, Ruoyun Wang, Renxiang Tan, Ming Fang, Bing Chen, Yinghong He, David C. S. Huang, Junyi Ju, Quan Zhao
shingle_author_2 Min Nie, Yadong Wang, Chan Guo, Xinyu Li, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Chi Ma, Ming Liu, Panxue Wang, Ruoyun Wang, Renxiang Tan, Ming Fang, Bing Chen, Yinghong He, David C. S. Huang, Junyi Ju, Quan Zhao
shingle_author_3 Min Nie, Yadong Wang, Chan Guo, Xinyu Li, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Chi Ma, Ming Liu, Panxue Wang, Ruoyun Wang, Renxiang Tan, Ming Fang, Bing Chen, Yinghong He, David C. S. Huang, Junyi Ju, Quan Zhao
shingle_author_4 Min Nie, Yadong Wang, Chan Guo, Xinyu Li, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Chi Ma, Ming Liu, Panxue Wang, Ruoyun Wang, Renxiang Tan, Ming Fang, Bing Chen, Yinghong He, David C. S. Huang, Junyi Ju, Quan Zhao
shingle_catch_all_1 CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
Protein arginine methyltransferase 5 (PRMT5) is a member of the arginine methyltransferase protein family that critically mediates the symmetric dimethylation of Arg-3 at histone H4 (H4R3me2s) and is involved in many key cellular processes, including hematopoiesis. However, the post-translational modifications (PTMs) of PRMT5 that may affect its biological functions remain less well-understood. In this study, using MS analyses, we found that PRMT5 itself is methylated in human erythroleukemia Lys-562 cells. Biochemical assays revealed that coactivator-associated arginine methyltransferase 1 (CARM1) interacts directly with and methylates PRMT5 at Arg-505 both in vivo and in vitro. Substitutions at Arg-505 significantly reduced PRMT5's methyltransferase activity, decreased H4R3me2s enrichment at the γ-globin gene promoter, and increased the expression of the γ-globin gene in Lys-562 cells. Moreover, CARM1 knockdown consistently reduced PRMT5 activity and activated γ-globin gene expression. Importantly, we show that CARM1-mediated methylation of PRMT5 is essential for the intracellular homodimerization of PRMT5 to its active form. These results thus reveal a critical PTM of PRMT5 that represses human γ-globin gene expression. We conclude that CARM1-mediated asymmetric methylation of PRMT5 is critical for its dimerization and methyltransferase activity leading to the repression of γ-globin expression. Given PRMT5's crucial role in diverse cellular processes, these findings may inform strategies for manipulating its methyltransferase activity for managing hemoglobinopathy or cancer.
Min Nie, Yadong Wang, Chan Guo, Xinyu Li, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Chi Ma, Ming Liu, Panxue Wang, Ruoyun Wang, Renxiang Tan, Ming Fang, Bing Chen, Yinghong He, David C. S. Huang, Junyi Ju, Quan Zhao
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_catch_all_2 CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
Protein arginine methyltransferase 5 (PRMT5) is a member of the arginine methyltransferase protein family that critically mediates the symmetric dimethylation of Arg-3 at histone H4 (H4R3me2s) and is involved in many key cellular processes, including hematopoiesis. However, the post-translational modifications (PTMs) of PRMT5 that may affect its biological functions remain less well-understood. In this study, using MS analyses, we found that PRMT5 itself is methylated in human erythroleukemia Lys-562 cells. Biochemical assays revealed that coactivator-associated arginine methyltransferase 1 (CARM1) interacts directly with and methylates PRMT5 at Arg-505 both in vivo and in vitro. Substitutions at Arg-505 significantly reduced PRMT5's methyltransferase activity, decreased H4R3me2s enrichment at the γ-globin gene promoter, and increased the expression of the γ-globin gene in Lys-562 cells. Moreover, CARM1 knockdown consistently reduced PRMT5 activity and activated γ-globin gene expression. Importantly, we show that CARM1-mediated methylation of PRMT5 is essential for the intracellular homodimerization of PRMT5 to its active form. These results thus reveal a critical PTM of PRMT5 that represses human γ-globin gene expression. We conclude that CARM1-mediated asymmetric methylation of PRMT5 is critical for its dimerization and methyltransferase activity leading to the repression of γ-globin expression. Given PRMT5's crucial role in diverse cellular processes, these findings may inform strategies for manipulating its methyltransferase activity for managing hemoglobinopathy or cancer.
Min Nie, Yadong Wang, Chan Guo, Xinyu Li, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Chi Ma, Ming Liu, Panxue Wang, Ruoyun Wang, Renxiang Tan, Ming Fang, Bing Chen, Yinghong He, David C. S. Huang, Junyi Ju, Quan Zhao
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_catch_all_3 CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
Protein arginine methyltransferase 5 (PRMT5) is a member of the arginine methyltransferase protein family that critically mediates the symmetric dimethylation of Arg-3 at histone H4 (H4R3me2s) and is involved in many key cellular processes, including hematopoiesis. However, the post-translational modifications (PTMs) of PRMT5 that may affect its biological functions remain less well-understood. In this study, using MS analyses, we found that PRMT5 itself is methylated in human erythroleukemia Lys-562 cells. Biochemical assays revealed that coactivator-associated arginine methyltransferase 1 (CARM1) interacts directly with and methylates PRMT5 at Arg-505 both in vivo and in vitro. Substitutions at Arg-505 significantly reduced PRMT5's methyltransferase activity, decreased H4R3me2s enrichment at the γ-globin gene promoter, and increased the expression of the γ-globin gene in Lys-562 cells. Moreover, CARM1 knockdown consistently reduced PRMT5 activity and activated γ-globin gene expression. Importantly, we show that CARM1-mediated methylation of PRMT5 is essential for the intracellular homodimerization of PRMT5 to its active form. These results thus reveal a critical PTM of PRMT5 that represses human γ-globin gene expression. We conclude that CARM1-mediated asymmetric methylation of PRMT5 is critical for its dimerization and methyltransferase activity leading to the repression of γ-globin expression. Given PRMT5's crucial role in diverse cellular processes, these findings may inform strategies for manipulating its methyltransferase activity for managing hemoglobinopathy or cancer.
Min Nie, Yadong Wang, Chan Guo, Xinyu Li, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Chi Ma, Ming Liu, Panxue Wang, Ruoyun Wang, Renxiang Tan, Ming Fang, Bing Chen, Yinghong He, David C. S. Huang, Junyi Ju, Quan Zhao
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_catch_all_4 CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
Protein arginine methyltransferase 5 (PRMT5) is a member of the arginine methyltransferase protein family that critically mediates the symmetric dimethylation of Arg-3 at histone H4 (H4R3me2s) and is involved in many key cellular processes, including hematopoiesis. However, the post-translational modifications (PTMs) of PRMT5 that may affect its biological functions remain less well-understood. In this study, using MS analyses, we found that PRMT5 itself is methylated in human erythroleukemia Lys-562 cells. Biochemical assays revealed that coactivator-associated arginine methyltransferase 1 (CARM1) interacts directly with and methylates PRMT5 at Arg-505 both in vivo and in vitro. Substitutions at Arg-505 significantly reduced PRMT5's methyltransferase activity, decreased H4R3me2s enrichment at the γ-globin gene promoter, and increased the expression of the γ-globin gene in Lys-562 cells. Moreover, CARM1 knockdown consistently reduced PRMT5 activity and activated γ-globin gene expression. Importantly, we show that CARM1-mediated methylation of PRMT5 is essential for the intracellular homodimerization of PRMT5 to its active form. These results thus reveal a critical PTM of PRMT5 that represses human γ-globin gene expression. We conclude that CARM1-mediated asymmetric methylation of PRMT5 is critical for its dimerization and methyltransferase activity leading to the repression of γ-globin expression. Given PRMT5's crucial role in diverse cellular processes, these findings may inform strategies for manipulating its methyltransferase activity for managing hemoglobinopathy or cancer.
Min Nie, Yadong Wang, Chan Guo, Xinyu Li, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Chi Ma, Ming Liu, Panxue Wang, Ruoyun Wang, Renxiang Tan, Ming Fang, Bing Chen, Yinghong He, David C. S. Huang, Junyi Ju, Quan Zhao
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_title_1 CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
shingle_title_2 CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
shingle_title_3 CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
shingle_title_4 CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
timestamp 2025-06-30T23:37:20.930Z
titel CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
titel_suche CARM1-mediated methylation of protein arginine methyltransferase 5 represses human {gamma}-globin gene expression in erythroleukemia cells [DNA and Chromosomes]
topic W
V
uid ipn_articles_6355791