PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing Journal Article
| Authors: | Zhao, Q.; Rank, G.; Tan, Y. T.; Li, H.; Moritz, R. L.; Simpson, R. J.; Cerruti, L.; Curtis, D. J.; Patel, D. J.; Allis, C. D.; Cunningham, J. M.; Jane, S. M. |
| Article Title: | PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing |
| Abstract: | Mammalian gene silencing is established through methylation of histones and DNA, although the order in which these modifications occur remains contentious. Using the human β-globin locus as a model, we demonstrate that symmetric methylation of histone H4 arginine 3 (H4R3me2s) by the protein arginine methyltransferase PRMT5 is required for subsequent DNA methylation. H4R3me2s serves as a direct binding target for the DNA methyltransferase DNMT3A, which interacts through the ADD domain containing the PHD motif. Loss of the H4R3me2s mark through short hairpin RNA-mediated knockdown of PRMT5 leads to reduced DNMT3A binding, loss of DNA methylation and gene activation. In primary erythroid progenitors from adult bone marrow, H4R3me2s marks the inactive methylated globin genes coincident with localization of PRMT5. Our findings define DNMT3A as both a reader and a writer of repressive epigenetic marks, thereby directly linking histone and DNA methylation in gene silencing. © 2009 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; protein domain; protein localization; protein motif; mammalia; gene targeting; models, biological; bone marrow; erythroid precursor cell; erythroid precursor cells; protein binding; gene locus; protein interaction; dna methylation; gene activation; epigenetics; globin gene; binding site; gene silencing; histones; short hairpin rna; gene knockdown techniques; protein interaction domains and motifs; dna (cytosine-5-)-methyltransferase; arginine; beta globin; dna methyltransferase 3a; histone h4; protein arginine methyltransferase; protein arginine methyltransferase 5; protein methyltransferases |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 16 |
| Issue: | 3 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-03-01 |
| Start Page: | 304 |
| End Page: | 311 |
| Language: | English |
| DOI: | 10.1038/nsmb.1568 |
| PUBMED: | 19234465 |
| PROVIDER: | scopus |
| PMCID: | PMC5120857 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 41" - "Export Date: 30 November 2010" - "CODEN: NSMBC" - "Source: Scopus" |
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