Methylation of Histone H4 at Arginine 3 Facilitating Transcriptional Activation by Nuclear Hormone Receptor
Hengbin Wang,1
Zhi-Qing Huang,2
Li Xia,1
Qin Feng,1
Hediye Erdjument-Bromage,3
Brian D. Strahl,4
Scott D. Briggs,4
C. David Allis,4
Jiemin Wong,2
Paul Tempst,3
Yi Zhang1*
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.
1 Department of Biochemistry and Biophysics,
Lineberger Comprehensive Cancer Center, University of North Carolina at
Chapel Hill, Chapel Hill, NC 27599-7295, USA.
2 Department of Molecular and Cellular Biology,
Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
3 Molecular Biology Program, Memorial Sloan
Kettering Cancer Center, New York, NY 10021, USA.
4 Department of Biochemistry and Molecular Genetics,
University of Virginia Health Science Center, Charlottesville, VA
22908, USA.
*
To whom correspondence should be addressed. E-mail:
yi_zhang{at}med.unc.edu
