Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1.
Posttranslational modifications of histone amino termini play an important role in modulating chromatin structure and function. Lysine methylation of histones has been well documented, and recently this modification has been linked to cellular processes involving gene transcription and heterochromatin assembly. However, the existence of arginine methylation on histones has remained unclear. Recent discoveries of protein arginine methyltransferases, CARM1 and PRMT1, as transcriptional coactivators for nuclear receptors suggest that histones may be physiological targets of these enzymes as part of a poorly defined transcriptional activation pathway. Here we show by using mass spectrometry that histone H4, isolated from asynchronously growing human 293T cells, is methylated at arginine 3 (Arg-3) in vivo. In support, a novel antibody directed against histone H4 methylated at Arg-3 independently demonstrates the in vivo occurrence of this modification and reveals that H4 Arg-3 methylation is highly conserved throughout eukaryotes. Finally, we show that PRMT1 is the major, if not exclusive, H4 Arg-3 methyltransfase in human 293T cells. These findings suggest a role for arginine methylation of histones in the transcription process.
Strahl
B D
BD
Department of Biochemistry and Molecular Genetics, University of Virginia Health Science Center, Charlottesville, VA 22908, USA.
Briggs
S D
SD
Brame
C J
CJ
Caldwell
J A
JA
Koh
S S
SS
Ma
H
H
Cook
R G
RG
Shabanowitz
J
J
Hunt
D F
DF
Stallcup
M R
MR
Allis
C D
CD
D020816:Amino Acid Motifs; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D017930:Genes, Reporter; D006657:Histones / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008745:Methylation; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D006657:Histones; D011993:Recombinant Fusion Proteins; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases