PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing
Details
Publication Year 2009-03, Volume 16, Issue #3, Page 304-311
Journal Title
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Publication Type
Journal Article
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 beta-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. (c) 2009 Nature America, Inc. All rights reserved.
Publisher
NATURE PUBLISHING GROUP
Keywords
BETA-GLOBIN LOCUS; GAMMA-GLOBIN; PHD FINGER; CHROMATIN-STRUCTURE; PLANT HOMEODOMAIN; BINDING MODULES; LINKS DNA; IN-VIVO; H3; LYSINE-4
Publisher's Version
https://doi.org/10.1038/nsmb.1568
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2009-03-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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