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 [1-3], Lysine methylati on of histones has been well documented [4, 5], and recently this modificat ion has been linked to cellular processes involving gene transcription and heterochromatin assembly [6-9]. However, the existence of arginine methylat ion on histones has remained unclear. Recent discoveries of protein arginin e methyltransferases, CARM1 and PRMT1, as transcriptional coactivators for nuclear receptors suggest that histones may be physiological targets of the se enzymes as part of a poorly defined transcriptional activation pathway [ 10-12], Here we show by using mass spectrometry that histone H4, isolated f rom asynchronously growing human 293T cells, is methylated at arginine 3 (A rg-3) in vivo. In support, a novel antibody directed against histone H4 met hylated at Arg-3 independently demonstrates the in vivo occurrence of this modification and reveals that H4 Arg-3 methylation is highly conserved thro ughout eukaryotes, Finally, we show that PRMT1 is the major, if not exclusi ve, H4 Arg-3 methyltransfase in human 293T cells. These findings suggest a role for arginine methylation of histones in the transcription process. (C) 2001 Elsevier Science Ltd. All rights reserved.