Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in vivo for many subsequent histone modifications.
PRMT1 is a histone methyltransferase that methylates Arg3 on histone H4. When we used siRNA to knock down PRMT1 in an erythroid cell line, it resulted in nearly complete loss of H4 Arg3 methylation across the chicken beta-globin domain, which we use as a model system for studying the relationship of gene activity to histone modification. We observed furthermore a domain-wide loss of histone acetylation on both histones H3 and H4, as well as an increase in H3 Lys9 and Lys27 methylation, both marks associated with inactive chromatin. To determine whether the effect on acetylation was directly related to the loss of H4 Arg3 methylation, we performed an in vitro acetylation reaction on chromatin isolated from PRMT1-depleted cells. We found that nucleosomes purified from these cells, and depleted in methylation at Arg3, are readily acetylated by nuclear extracts from the same cells, if and only if the nucleosomes are incubated with PRMT1 beforehand. Thus, methylation of histones by PRMT1 was sufficient to permit subsequent acetylation. Consistent with earlier reports of experiments in vitro, H4 Arg3 methylation by PRMT1 appears to be essential in vivo for the establishment or maintenance of a wide range of "active" chromatin modifications.
Huang
Suming
S
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0540, USA.
Litt
Michael
M
Felsenfeld
Gary
G
D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002645:Chickens; D041905:Erythroid Cells / Q000166:cytology; D005914:Globins / Q000235:genetics; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology*; D034741:RNA, Small Interfering; D014158:Transcription, Genetic / Q000502:physiology
D006570:Heterochromatin; D006657:Histones; D034741:RNA, Small Interfering; D005914:Globins; D011484:Protein-Arginine N-Methyltransferases