Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor

Acetylation of core histone tails plays a fundamental role in transcription regulation. In addition to acetylation, other posttranslational modificati ons, such as phosphorylation and methylation, occur in core histone tails. Here, we report the purification, molecular identification, and functional characterization of a histone H4-specific methyltransferase PRMT1, a protei n arginine methyltransferase. PRMT1 specifically methylates arginine 3 (Arg 3) of H4 in vitro and in vivo. Methylation of Arg 3 by PRMT1 facilitates s ubsequent acetylation of H4 tails by p300. However, acetylation of H4 inhib its its methylation by PRMT1. Most important, a mutation in the S-adenosyl- L-methionine-binding site of PRMT1 substantially crippled its nuclear recep tor coactivator activity. Our finding reveals Arg 3 of H4 as a novel methyl ation site by PRMT1 and indicates that Arg 3 methylation plays an important role in transcriptional regulation.