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Science 293 (5531): 853-857

Copyright © 2001 by the American Association for the Advancement of Science

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}

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Hepatitis Delta Virus Antigen Is Methylated at Arginine Residues, and Methylation Regulates Subcellular Localization and RNA Replication.
Y.-J. Li, M. R. Stallcup, and M. M. C. Lai (2004)
J. Virol. 78, 13325-13334
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Arginine Methylation of Scaffold Attachment Factor A by Heterogeneous Nuclear Ribonucleoprotein Particle-associated PRMT1.
F. Herrmann, M. Bossert, A. Schwander, E. Akgun, and F. O. Fackelmayer (2004)
J. Biol. Chem. 279, 48774-48779
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Human SWI/SNF-Associated PRMT5 Methylates Histone H3 Arginine 8 and Negatively Regulates Expression of ST7 and NM23 Tumor Suppressor Genes.
S. Pal, S. N. Vishwanath, H. Erdjument-Bromage, P. Tempst, and S. Sif (2004)
Mol. Cell. Biol. 24, 9630-9645
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Human PAD4 Regulates Histone Arginine Methylation Levels via Demethylimination.
Y. Wang, J. Wysocka, J. Sayegh, Y.-H. Lee, J. R. Perlin, L. Leonelli, L. S. Sonbuchner, C. H. McDonald, R. G. Cook, Y. Dou, et al. (2004)
Science 306, 279-283
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Epigenetics and cancer.
A. H. Lund and M. van Lohuizen (2004)
Genes & Dev. 18, 2315-2335
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Transcriptional complexes engaged by apo-estrogen receptor-{alpha} isoforms have divergent outcomes.
R. Metivier, G. Penot, R. P. Carmouche, M. R. Hubner, G. Reid, S. Denger, D. Manu, H. Brand, M. Kos, V. Benes, et al. (2004)
EMBO J. 23, 3653-3666
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Dynamic alterations of specific histone modifications during early murine development.
O. F. Sarmento, L. C. Digilio, Y. Wang, J. Perlin, J. C. Herr, C. D. Allis, and S. A. Coonrod (2004)
J. Cell Sci. 117, 4449-4459
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A Histone Methyltransferase Is Required for Maximal Response to Female Sex Hormones.
T. Carling, K.-C. Kim, X.-H. Yang, J. Gu, X.-K. Zhang, and S. Huang (2004)
Mol. Cell. Biol. 24, 7032-7042
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Cluster Analysis of Mass Spectrometry Data Reveals a Novel Component of SAGA.
D. W. Powell, C. M. Weaver, J. L. Jennings, K. J. McAfee, Y. He, P. A. Weil, and A. J. Link (2004)
Mol. Cell. Biol. 24, 7249-7259
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Small Molecule Regulators of Protein Arginine Methyltransferases.
D. Cheng, N. Yadav, R. W. King, M. S. Swanson, E. J. Weinstein, and M. T. Bedford (2004)
J. Biol. Chem. 279, 23892-23899
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Mechanistic Relationship between Androgen Receptor Polyglutamine Tract Truncation and Androgen-dependent Transcriptional Hyperactivity in Prostate Cancer Cells.
Q. Wang, T. S. Udayakumar, T. S. Vasaitis, A. M. Brodie, and J. D. Fondell (2004)
J. Biol. Chem. 279, 17319-17328
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Transcription Factors and Nuclear Receptors Interact with the SWI/SNF Complex through the BAF60c Subunit.
M.-B. Debril, L. Gelman, E. Fayard, J.-S. Annicotte, S. Rocchi, and J. Auwerx (2004)
J. Biol. Chem. 279, 16677-16686
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Lessons from the Genome Sequence of Neurospora crassa: Tracing the Path from Genomic Blueprint to Multicellular Organism.
K. A. Borkovich, L. A. Alex, O. Yarden, M. Freitag, G. E. Turner, N. D. Read, S. Seiler, D. Bell-Pedersen, J. Paietta, N. Plesofsky, et al. (2004)
Microbiol. Mol. Biol. Rev. 68, 1-108
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Linking Covalent Histone Modifications to Epigenetics: The Rigidity and Plasticity of the Marks.
Cold Spring Harb Symp Quant Biol 69, 161-170
   Abstract »    PDF »

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