Reports

Recognition of Histone H3 Lysine-4 Methylation by the Double Tudor Domain of JMJD2A

Ying Huang,^1* Jia Fang,² Mark T. Bedford,³ Yi Zhang,² Rui-Ming Xu^1*

Biological responses to histone methylation critically depend on the faithful readout and transduction of the methyl-lysine signal by "effector" proteins, yet our understanding of methyl-lysine recognition has so far been limited to the study of histone binding by chromodomain and WD40-repeat proteins. The double tudor domain of JMJD2A, a Jmjc domain–containing histone demethylase, binds methylated histone H3-K4 and H4-K20. We found that the double tudor domain has an interdigitated structure, and the unusual fold is required for its ability to bind methylated histone tails. The cocrystal structure of the JMJD2A double tudor domain with a trimethylated H3-K4 peptide reveals that the trimethyl-K4 is bound in a cage of three aromatic residues, two of which are from the tudor-2 motif, whereas the binding specificity is determined by side-chain interactions involving amino acids from the tudor-1 motif. Our study provides mechanistic insights into recognition of methylated histone tails by tudor domains and reveals the structural intricacy of methyl-lysine recognition by two closely spaced effector domains.

¹ W. M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
² Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599–7295, USA.
³ The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Post Office Box 389, Smithville, TX 78957, USA.

^* Present address: Structural Biology Program, Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA.

To whom correspondence should be addressed. E-mail: rmxu{at}saturn.med.nyu.edu

Read the Full Text

Identification of Chromatin Remodeling Genes Arid4a and Arid4b as Leukemia Suppressor Genes.

M.-Y. Wu, K. W. Eldin, and A. L. Beaudet (2008)
J Natl Cancer Inst 100, 1247-1259
 |  Abstract »  |  Full Text »  |  PDF »

Inferring causal relationships among different histone modifications and gene expression.

H. Yu, S. Zhu, B. Zhou, H. Xue, and J.-D. J. Han (2008)
Genome Res. 18, 1314-1324
 |  Abstract »  |  Full Text »  |  PDF »

Protein Methyltransferase Activities in Commercial In vitro Translation Systems.

R. B. Denman (2008)
J. Biochem. 144, 223-233
 |  Abstract »  |  Full Text »  |  PDF »

Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease.

P. A.C. Cloos, J. Christensen, K. Agger, and K. Helin (2008)
Genes & Dev. 22, 1115-1140
 |  Abstract »  |  Full Text »  |  PDF »

Co- and post-translational modifications in Rubisco: unanswered questions.

R. L. Houtz, R. Magnani, N. R. Nayak, and L. M. A. Dirk (2008)
J. Exp. Bot. 59, 1635-1645
 |  Abstract »  |  Full Text »  |  PDF »

Role of hPHF1 in H3K27 Methylation and Hox Gene Silencing.

R. Cao, H. Wang, J. He, H. Erdjument-Bromage, P. Tempst, and Y. Zhang (2008)
Mol. Cell. Biol. 28, 1862-1872
 |  Abstract »  |  Full Text »  |  PDF »

Arginine Methylation of the Histone H3 Tail Impedes Effector Binding.

A. N. Iberg, A. Espejo, D. Cheng, D. Kim, J. Michaud-Levesque, S. Richard, and M. T. Bedford (2008)
J. Biol. Chem. 283, 3006-3010
 |  Abstract »  |  Full Text »  |  PDF »

Structure and Mechanism of Lysine-specific Demethylase Enzymes.

R. Anand and R. Marmorstein (2007)
J. Biol. Chem. 282, 35425-35429
 |  Abstract »  |  Full Text »  |  PDF »

The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2.

S. Ramon-Maiques, A. J. Kuo, D. Carney, A. G. W. Matthews, M. A. Oettinger, O. Gozani, and W. Yang (2007)
PNAS 104, 18993-18998
 |  Abstract »  |  Full Text »  |  PDF »

Tudor Nuclease Genes and Programmed DNA Rearrangements in Tetrahymena thermophila.

R. A. Howard-Till and M.-C. Yao (2007)
Eukaryot. Cell 6, 1795-1804
 |  Abstract »  |  Full Text »  |  PDF »

Two Saccharomyces cerevisiae JmjC Domain Proteins Demethylate Histone H3 Lys36 in Transcribed Regions to Promote Elongation.

T. Kim and S. Buratowski (2007)
J. Biol. Chem. 282, 20827-20835
 |  Abstract »  |  Full Text »  |  PDF »

Structural basis of the recognition of a methylated histone tail by JMJD2A.

Z. Chen, J. Zang, J. Kappler, X. Hong, F. Crawford, Q. Wang, F. Lan, C. Jiang, J. Whetstine, S. Dai, et al. (2007)
PNAS 104, 10818-10823
 |  Abstract »  |  Full Text »  |  PDF »

HULC, a Histone H2B Ubiquitinating Complex, Modulates Heterochromatin Independent of Histone Methylation in Fission Yeast.

M. Zofall and S. I. S. Grewal (2007)
J. Biol. Chem. 282, 14065-14072
 |  Abstract »  |  Full Text »  |  PDF »

Histone Modification Pattern of the T-Cellular Herpesvirus Saimiri Genome in Latency.

B. Alberter and A. Ensser (2007)
J. Virol. 81, 2524-2530
 |  Abstract »  |  Full Text »  |  PDF »

The Yng1p Plant Homeodomain Finger Is a Methyl-Histone Binding Module That Recognizes Lysine 4-Methylated Histone H3.

D. G. E. Martin, K. Baetz, X. Shi, K. L. Walter, V. E. MacDonald, M. J. Wlodarski, O. Gozani, P. Hieter, and L. Howe (2006)
Mol. Cell. Biol. 26, 7871-7879
 |  Abstract »  |  Full Text »  |  PDF »

Histone H3 Lys 4 methylation: caught in a bind?.

R. J. Sims III and D. Reinberg (2006)
Genes & Dev. 20, 2779-2786
 |  Full Text »  |  PDF »

The role of Tudor domains in germline development and polar granule architecture.

A. L. Arkov, J.-Y. S. Wang, A. Ramos, and R. Lehmann (2006)
Development 133, 4053-4062
 |  Abstract »  |  Full Text »  |  PDF »

Epigenetic regulators and histone modification.

A. Imhof (2006)
Brief Funct Genomic Proteomic 5, 222-227
 |  Abstract »  |  Full Text »  |  PDF »

ADVERTISEMENT

ADVERTISEMENT

To Advertise   |   Find Products