title: Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor.
abstract: Acetylation of core histone tails plays a fundamental role in transcription regulation. In addition to acetylation, other posttranslational modifications, 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 protein arginine methyltransferase. PRMT1 specifically methylates arginine 3 (Arg 3) of H4 in vitro and in vivo. Methylation of Arg 3 by PRMT1 facilitates subsequent acetylation of H4 tails by p300. However, acetylation of H4 inhibits its methylation by PRMT1. Most important, a mutation in the S-adenosyl-l-methionine-binding site of PRMT1 substantially crippled its nuclear receptor coactivator activity. Our finding reveals Arg 3 of H4 as a novel methylation site by PRMT1 and indicates that Arg 3 methylation plays an important role in transcriptional regulation.
authors.affiliation: Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Huang
authors.forename: L
authors.initials: L
authors.lastname: Xia
authors.forename: Q
authors.initials: Q
authors.lastname: Feng
authors.forename: H
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: B D
authors.initials: BD
authors.lastname: Strahl
authors.forename: S D
authors.initials: SD
authors.lastname: Briggs
authors.forename: C D
authors.initials: CD
authors.lastname: Allis
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.forename: P
authors.initials: P
authors.lastname: Tempst
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes; D011484:Protein-Arginine N-Methyltransferases; D011944:Receptors, Androgen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D015533:Transcriptional Activation; D014981:Xenopus
chemical_list: D006657:Histones; D006877:Hydroxamic Acids; D047908:Intracellular Signaling Peptides and Proteins; D011944:Receptors, Androgen; D011994:Recombinant Proteins; C012589:trichostatin A; D012436:S-Adenosylmethionine; D001120:Arginine; D008780:Methyltransferases; C077013:PRMT2 protein, human; D011484:Protein-Arginine N-Methyltransferases; D008239:Lysine