![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RESEARCH COMMUNICATION
1 W.M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA , 2 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599, USA
 |
Abstract |
|---|
 Top Abstract Results and DiscussionMaterials and methodsAcknowledgmentsReferences |
|---|
[Keywords: Chromatin; histone code; histone methylation; Polycomb; chromodomain]
Received April 22, 2003; revised version accepted June 5, 2003.
;
Turner 2000). In particular,
histone methylation has been shown to mediate diverse biological processes
such as heterochromatin formation, X chromosome inactivation, and
transcriptional regulation (Grewal and
Elgin 2002). Several SET-domain histone lysine methyltransferases
have been identified (Zhang and Reinberg
2001; Lachner and Jenuwein
2002): They methylate various lysine residues located at the
flexible N termini of histones H3 and H4. Methylation of different lysine
residues has differential biological effects. To decipher the histone code
generated by lysine methylation, it is important to understand the mechanism
by which the various methyl-lysine signals are differentially recognized by
the cellular machinery.
Two well-studied chromatin-regulated biological processes are position
effect variegation (PEV) and homeotic gene silencing in Drosophila.
Heterochromatin formation in PEV is associated with methylation of Lys 9 of
histone H3 by SU(VAR)3-9 and its homologs
(Rea et al. 2000). Methylation
of Lys 27 of histone H3 by a multiprotein complex containing Enhancer of
Zeste, E(z), and Extra Sex Combs (ESC), or their human counterparts EZH2 and
EED, are associated with the repression of homeotic genes
(Cao et al. 2002;
Czermin et al. 2002;
Kuzmichev et al. 2002;
Muller et al. 2002) as well as
with the inactive X chromosome (Plath et
al. 2003; Silva et al.
2003). Interestingly, Lys 9 methylation has also been reported as
an early marker on the inactive X chromosome
(Heard et al. 2001).
Methylation of Lys 9 and Lys 27 of histone H3 creates binding sites for the
chromodomains of HP1 and Polycomb (PC) proteins, respectively
(Bannister et al. 2001;
Lachner et al. 2001;
Nakayama et al. 2001;
Cao et al. 2002;
Czermin et al. 2002;
Kuzmichev et al. 2002;
Muller et al. 2002).
Chromodomains were originally identified as a conserved sequence motif between
PC and HP1 (Paro and Hogness
1991), although the chromodomain protein family has expanded
considerably since the original identification
(Eissenberg 2001). The
chromodomain of PC alone is fully functional in nuclear localization and
chromosome binding (Messmer et al.
1992). Despite the high sequence homology between the two
chromodomains, PC and HP1 bind to distinct chromosomal loci
(James et al. 1989;
Zink and Paro 1989), and the
molecular mechanisms of locus specific recruitment of PC and HP1 remain poorly
understood.
The structure of the HP1 chromodomain in complex with a methyl-Lys 9
histone H3 peptide has been determined recently
(Jacobs and Khorasanizadeh
2002; Nielsen et al.
2002). The structure greatly advanced our understanding of
methylated histone tail-chromodomain interactions. However, the HP1 structure
offered no insights into the molecular mechanism of specific binding of the
highly homologous PC chromodomain to histone H3 tails methylated at Lys 27.
Here we report a 1.4-Å-resolution structure of the Drosophila
Polycomb (dPC) chromodomain in complex with a histone H3 peptide trimethylated
at Lys 27 (m3K27). The structure shows a conserved mode of
methyl-lysine recognition and reveals key elements in histone H3 and dPC that
can account for the binding specificity. In particular, crystal packing of two
dPC molecules via evolutionarily conserved residues gives rise to an
interesting model that the chromodomain of dPC functions as a dimer. This
model agrees well with in vitro chemical cross-linking and in vivo domain swap
results; it predicts that histone-histone interactions are important for the
selective binding of the histone H3 tail to dPC, and dPC facilitates homeotic
gene silencing by mediating interactions of nucleosomes methylated at Lys
27.
|
Results and Discussion |
|---|
|
TopAbstractResults and DiscussionMaterials and methodsAcknowledgmentsReferences |
|---|
/
angles
are within the most favored region and none in the disallowed region of the
Ramachandran plot, calculated using PROCHECK
(Laskowski et al. 1993).
Detailed statistics of the crystallographic analysis are shown in
Table 1.
|
|
Chromodomain-histone interactions
The dPC chromodomain consists of three 
-strands (1-3)
that form a twisted antiparallel -sheet. A helix (
A) located at
the C-terminal end is packed against one edge of the -sheet next to
1 (Fig. 1B). The histone
H3 peptide is bound in a cleft formed between a segment of dPC N-terminal to
1 and the loop connecting 3 and A. Consistent with the high
sequence homology of PC and HP1 chromodomains
(Fig. 2A), the overall
structures of the dPC and HP1 chromodomains are very similar
(Jacobs and Khorasanizadeh
2002; Nielsen et al.
2002). The C positions of dPC and HP1
chromodomains can be aligned with a root-mean-squared deviation (RMSD) of 1.1
Å, and the two peptides (amino acids 5-10 and 23-28 of histone H3) can
be aligned with an RMSD of 0.45 Å. Many features of the interactions
between dPC and the H3m3K27 peptide are also similar to that
between HP1 and H3m3K9 peptides. First, m3K27 is bound
in a hydrophobic pocket formed by three aromatic residues, Tyr 26, Trp 47, and
Trp 50 (Fig. 1A). Second, the
main-chain carbonyl and amino groups of Lys 23, Ala 24, Ala 25, and Arg 26 of
the H3m3K27 peptide are involved in -sheet-like hydrogen
bonding with dPC residues 24-28 located at the N terminus and residues 62-65
located in the loop connecting 3 and A
(Fig. 2B). Third, the hydroxyl
group of Ser 28 of histone H3 makes hydrogen bonds to Glu 58 and Asn 62
(Fig. 2B). Fourth, Ala 25 of
histone H3 is buried in a shallow hydrophobic pocket surrounded by Ala 28, Trp
47, Ile 63, and Leu 68.
|
One noticeable difference between the structures of dPC and HP1 occurs in
the methyl-lysine binding pocket, in which m3K9 or m3K27
interact with three aromatic residues via hydrophobic and cation-
interactions. In the HP1 structure, the residue corresponding to Trp 50 of dPC
is a tyrosine or phenylalanine (Fig.
2A). The conformation of Trp 50 is stabilized by the presence of
Tyr 54, which packs against Trp 50 with its ring approximately perpendicular
to that of Trp 50. The side chain of Tyr 54 does not interact with
m3K27 directly or via water molecules, whereas the corresponding
residue in HP1 interacts with m3K9 either directly or via a water
molecule (Jacobs and Khorasanizadeh
2002; Nielsen et al.
2002). In the dPC structure, the
C
—N
bond of m3K27 points to
the center of the six-carbon ring of Trp 50, and the distance between the
N atom of m3K27 and the center of the six-carbon
ring is 4.1 Å (Fig. 1A). This geometric arrangement enables a favorable cation- interaction between
the methylammonium group of m3K27 and Trp 50. In the HP1
structures, the C—N bond of
m3K9 is not lined up with the center of the phenyl ring
(Jacobs and Khorasanizadeh
2002; Nielsen et al.
2002), which results in a less-than-optimal cation-
interaction between m3K9 and the tyrosine or phenylalanine.
Leu 20 and Thr 22 of histone H3 are involved in unique interactions with Arg 67 of dPC. The carbonyl groups of Leu 20 and Thr 22 form hydrogen bonds with the side chain NH2 groups of Arg 67 (Fig. 2C). The conformation of Arg 67 is stabilized by two hydrogen bonds with the side chain of Asp 65, which itself interacts with the H3m3K27 peptide via main-chain hydrogen bonding as described earlier. Although both Arg 67 and Asp 65 are specifically conserved in PC chromodomains (Fig. 2A), and the observed interactions are not present in the HP1-H3m3K9 complex, the interactions between Arg 67 and Leu 20 and Thr 22 of H3m3K27 cannot account for the binding specificity as only the main-chain atoms of histone H3 are involved in the interactions.
Polycomb binding specificity
It is puzzling that the PC-specific interactions identified above are
through the main-chain atoms of the histone H3 peptide, as they provide no
clear answers to the apparent in vitro binding preferences of dPC and HP1
(Cao et al. 2002;
Czermin et al. 2002;
Kuzmichev et al. 2002). A
careful examination of the structure identifies a potential chromodomain dimer
that can account for the binding specificity of dPC
(Fig. 3). The dimer is formed
across the crystal lattice, which at first sight might be discounted as a
crystal-packing artifact. However, the following reasons prompt us to examine
the dimeric interaction in detail: (1) The residues involved in the
protein-protein interaction are specifically conserved in the Polycomb family
of proteins. (2) There are very few solvent molecules at the interface of the
two dPC complexes. (3) Dynamic light scattering in solution shows that the
chromodomain of dPC has an apparent molecular mass of 14.2 kD, which is close
to twice the 6.8 kD calculated mass of a monomer. (4) A dPC chromodomain dimer
is consistent with previous in vivo domain-swap
(Platero et al. 1995) and in
vitro chemical cross-linking studies
(Cowell and Austin 1997).
|
It is interesting to note that the HP1 chromodomain apparently exists as a
monomer (Jacobs and Khorasanizadeh
2002; Nielsen et al.
2002), although the full-length protein is known to oligomerize
via the C-terminal chromo shadow domain
(Brasher et al. 2000;
Cowieson et al. 2000). In the
crystal structure of the chromodomain of dPC, the two monomers are located
across two adjacent asymmetric units. The two chromodomains of dPC in the
dimer interact via intermolecular hydrogen bonds between the main-chain atoms
of Leu 64 and Arg 66 (Fig. 3A).
Additionally, the N
1 atom of Arg 66 makes one
hydrogen bond with the carbonyl of Val 61. Leu 64 is specifically conserved in
the PC family of proteins, whereas Arg 66 and Val 61 are not. However, the two
main-chain hydrogen bonds between Leu 64 and Arg 66 appear to be specific to
the PC family of proteins. This is because the side chain of Cys 63 of HP1
(Drosophila HP1 numbering) is packed in a hydrophobic core, whereas
the corresponding residue in dPC, Asp 65, is excluded from a similar
hydrophobic environment. The packing of Cys 63 of HP1 causes an alteration of
the main-chain conformation that prevents the formation of similar
intermolecular hydrogen bonding. Both Asp 65 of dPC and Cys 63 of HP1 are
specifically conserved in their respective chromodomain subfamilies
(Fig. 2A).
The dPC chromodomain dimer juxtaposes the two H3-binding clefts in an
antiparallel fashion and results in histone-histone interactions involving Leu
20, Thr 22, and Ala 24 of histone H3 (Figs.
3,
4). In the structure, Arg 67 of
dPC stabilizes the N-terminal region of the histone H3 peptide through
hydrogen bonding of its N atoms with the histone H3 carbonyl
groups of Leu 20 and Thr 22 (Fig.
2C). These interactions position the side chain of Leu 20 in a
mostly hydrophobic pocket formed by the side chains of Val 25, Tyr 26, and Ala
27 of another PC molecule in the dimer, and the side chains of Thr 22 and Ala
24 of the other histone H3 peptide (Fig.
4). This recognition mode can effectively exclude the binding of a
histone H3 peptide encompassing methylated Lys 9, as the residues
corresponding to Leu 20, Thr 22, and Ala 24 of histone H3 would be Arg 2, Lys
4, and Thr 5, respectively. Figure
4 shows that replacing Leu 20 and Thr 22 with an arginine and a
lysine, respectively, will introduce steric conflicts and is strongly
disfavored from an energetic standpoint. Thus, both the histone H3 sequence at
positions 20, 22, 24, and the dimerization of the chromodomain of dPC are key
determinants for the recognition of the histone H3 methyl-Lys 27 code.
|
Structural implications
The crystal structure presented here shows that the chromodomains of dPC and HP1 have a common overall structure, and they also bind methyl-lysine-containing substrates similarly. The structure identifies that Arg 67 and Asp 65 of dPC are important for Polycomb-specific interactions with histone H3. Curiously, these residues interact with the main chain of the histone peptide. This is also true in the HP1 structure, where most of the chromodomain-histone interactions are through main-chain atoms. An important question concerning the recognition of the methylated histone tail by Polycomb and HP1 is what determines their binding specificities. The difference in histone-binding affinity of Polycomb and HP1 is not sufficient to account for their substrate specificities. Our crystallographic analyses have identified a dPC chromodomain dimer in the crystal lattice that can account for the binding specificity of dPC, and we have outlined compelling reasons in support of the potential physiological significance of the observed dimeric interactions.
Although dimerization of dPC was never pointed out explicitly before,
self-association of the PC chromodomain was noted in several previous studies
(Platero et al. 1995;
Cowell and Austin 1997).
Interestingly, an in vivo domain-swap experiment replacing the chromodomain of
HP1 with that of dPC showed that the chimeric protein binds to both
heterochromatin and dPC binding sites in polytene chromosomes
(Platero et al. 1995).
Furthermore, some endogenous dPC is misdirected to the heterochromatic center,
whereas some endogenous HP1 is mislocalized to the dPC binding sites. These
observations not only confirmed earlier observations that the chromodomain of
dPC and the C-terminal chromo shadow domain of HP1 possess intrinsic nuclear
localization and chromosomal binding properties
(Messmer et al. 1992;
Powers and Eissenberg 1993),
they also indicated that the dPC chromodomain directs the mislocalization of
endogenous dPC through protein-protein contacts.
The dimerization model predicts that the binding specificity of the dPC
chromodomain arises from histone-histone interactions resulting from the close
proximity of the two histone-tail-binding sites in the dPC chromodomain dimer.
We pointed out earlier that the binding of two methyl-Lys9 histone H3 tails by
the dPC chromodomain dimer is disallowed because of potential steric clashes.
It is possible that the dPC chromodomain dimer may bind only one histone H3
tail in some instances. In this case, the available structural information
cannot exclude the binding of a methyl-Lys9 histone H3 tail to the dPC
chromodomain dimer. The observation by several groups that the PC chromodomain
binds specifically to methyl-27 histone H3 peptides in vitro clearly supports
the binding of two histone H3 tails to the dPC dimer
(Cao et al. 2002;
Czermin et al. 2002;
Kuzmichev et al. 2002). The
structure also provides insights into the function of PC proteins in the
assembly of repressive higher-order chromatin structure. Because the two
histone H3-binding sites are closely juxtaposed, the two histone tails are
unlikely to come from the same nucleosome. In the nucleosome core particle
structure (Luger et al. 1997),
Lys 27 is ordered in one of the H3 tails, whereas the ordered residues start
from Pro 38 in the other H3 molecule. The observed distance between the
C atoms of Pro 38 and Lys 27 of the same H3 molecule is 26
Å. The two histone-H3 Pro 38 residues are 73 Å apart (linear
distance) in the nucleosome core particle structure, which coverts to 
80
Å along the arc of wrapped DNA. The two Lys 27 C atoms
must be within 27 Å to occupy the two binding sites in the dPC
chromodomain dimer. Assuming that the two H3 tails N-terminal to Pro 38 can be
maximally stretched and free to adopt any conformation, we still cannot model
the simultaneous binding of two histone tails from the same nucleosome to the
dPC chromodomain dimer without steric clashes. Thus, we believe that the
histone tails binding to the dPC chromodomain dimer must come from two
separate nucleosomes. The in vivo binding of two methyl-Lys 27 histone-H3
tails, from spatially adjacent nucleosomes, will effectively lock the
nucleosomes into a more compact configuration. This compaction will lead to a
repressive chromatin state associated with the silencing of homeotic genes. A
similar function for HP1 in the assembly of heterochromatin has been proposed,
although dimerization of HP1 via the C-terminal chromo shadow domain makes the
binding of two histone tails from the same nucleosome, as well as separate
ones, possible.
|
Materials and methods |
|---|
|
TopAbstractResults and DiscussionMaterials and methodsAcknowledgmentsReferences |
|---|
15 mg/mL in a buffer containing 5 mM Tris (pH
8.0), 200 mM NaCl, 1 mM EDTA, and 1 mM DTT. A solution dynamic
light-scattering study (at 5 mg/mL) shows that dPC exists as a
homogeneous species with an apparent molecular mass of 14.2 kD. The calculated
molecular mass of a dPC (amino acids 23-77) monomer is 6.8 kD. We interpreted
that dPC may exist as a dimer in solution under the conditions tested. For
cocrystallization, chemically synthesized histone H3 peptide (amino acids
19-33) trimethylated at Lys 27 was mixed with dPC (15 mg/mL final
concentration) in an 1:1 (histone peptide vs. dPC monomer) molar ratio
prior to crystallization. The mixture was incubated on ice for 1 h to allow
complex formation. The crystal of the dPC-H3 peptide complex was grown by
hanging-drop vapor diffusion at 16°C in a condition containing 100 mM
sodium cacodylate (pH 6.5), 0.2 M ammonium sulfate, 30% PEG-8k, and 10 mM
DTT.
X-ray diffraction data were collected at 95°K using a CCD detector
(ADSC) at beamline X26C of the National Synchrotron Light Source, Brookhaven
National Laboratory. Raw data were processed using the HKL software package
(Otwinowski and Minor 1997).
The crystal has I21212
[GenBank]
1 symmetry and unit cell dimensions of 32.43 Å
x 77.03 Å x 77.27 Å. The structure was solved by
molecular replacement using the program AmoRe
(Navaza 2001). The crystal
structure of the Drosophila HP1 chromodomain
(Jacobs and Khorasanizadeh
2002) was used as the search model (the methyl-Lys 9 histone H3
peptide was omitted). An initial dPC model based on the molecular replacement
solution was subjected to automatic main-chain tracing and side-chain docking
using ARP/warp (Perrakis et al.
1999). The H3 peptide structure was built manually. The graphics
program O (Jones et al. 1991)
was used for model building and visualization. The structure was refined using
CNS (Brunger et al. 1998).
Detailed statistics of the crystallographic analysis can be found in
Table 1. Figures were prepared
using PyMol (DeLano 2002),
Molscript (Kraulis 1991),
Raster3D (Merritt and Bacon
1997), and Grasp (Nicholls et
al. 1991).
The PDB accession code is 1PFB.
|
Acknowledgments |
|---|
|
TopAbstractResults and DiscussionMaterials and methodsAcknowledgmentsReferences |
|---|
The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.
|
Footnotes |
|---|
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.269603.
3 E-MAIL
xur{at}cshl.org;
FAX (516) 367-8873. 
|
References |
|---|
|
TopAbstractResults and DiscussionMaterials and methodsAcknowledgmentsReferences |
|---|
Brasher, S.V., Smith, B.O., Fogh, R.H., Nietlispach, D., Thiru, A., Nielsen, P.R., Broadhurst, R.W., Ball, L.J., Murzina, N.V., and Laue, E.D. 2000. The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer. EMBO J. 19: 1587-1597.[CrossRef][Medline]
Brunger, A.T., Adams, P.D., Clore, G.M., DeLano, W.L., Gros, P., Grosse-Kunstleve, R.W., Jiang, J.S., Kuszewski, J., Nilges, M., Pannu, N.S., et al. 1998. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D 54: 905-921.[CrossRef][Medline]
Cao, R., Wang, L.,
Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R.S., and Zhang,
Y. 2002. Role of histone H3 lysine 27 methylation in
Polycomb-group silencing. Science
298:
1039-1043.
Cowell, I.G. and Austin, C.A. 1997. Self-association of chromo domain peptides. Biochim. Biophys. Acta 1337: 198-206.[CrossRef][Medline]
Cowieson, N.P., Partridge, J.F., Allshire, R.C., and McLaughlin, P.J. 2000. Dimerisation of a chromo shadow domain and distinctions from the chromodomain as revealed by structural analysis. Curr. Biol. 10: 517-525.[CrossRef][Medline]
Czermin, B., Melfi, R., McCabe, D., Seitz, V., Imhof, A., and Pirrotta, V. 2002. Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 111: 185-196.[CrossRef][Medline]
Delano, W.L. 2002. The PyMOL molecular graphics system. DeLano Scientific, San Carlos, CA.
Eissenberg, J.C. 2001. Molecular biology of the chromo domain: An ancient chromatin module comes of age. Gene 275: 19-29.[CrossRef][Medline]
Grewal, S.I. and Elgin, S.C. 2002. Heterochromatin: New possibilities for the inheritance of structure. Curr. Opin. Genet. Dev. 12: 178-187.[CrossRef][Medline]
Heard, E., Rougeulle, C., Arnaud, D., Avner, P., Allis, C.D., and Spector, D.L. 2001. Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation. Cell 107: 727-738.[CrossRef][Medline]
Jacobs, S.A. and
Khorasanizadeh, S. 2002. Structure of HP1 chromodomain bound to a
lysine 9-methylated histone H3 tail. Science
295:
2080-2083.
James, T.C., Eissenberg, J.C., Craig, C., Dietrich, V., Hobson, A., and Elgin, S.C. 1989. Distribution patterns of HP1, a heterochromatin-associated nonhistone chromosomal protein of Drosophila. Eur. J. Cell Biol. 50: 170-180.[Medline]
Jones, T.A., Zou, J.Y., Cowan, S.W., and Kjeldgaard, M. 1991. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47: 110-119.
Kraulis, P.J. 1991. Molscript—A program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24: 946-950.[CrossRef]
Kuzmichev, A.,
Nishioka, K., Erdjument-Bromage, H., Tempst, P., and Reinberg, D.
2002. Histone methyltransferase activity associated with a human
multiprotein complex containing the Enhancer of Zeste protein.
Genes & Dev. 16:
2893-2905.
Lachner, M. and Jenuwein, T. 2002. The many faces of histone lysine methylation. Curr. Opin. Cell Biol. 14: 286-298.[CrossRef][Medline]
Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., and Jenuwein, T. 2001. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410: 116-120.[CrossRef][Medline]
Laskowski, R.A., MacArthur, M.W., Moss, D.S., and Thornton, J.M. 1993. PROCHECK: A program to produce both detailed and schematic plots of proteins. J. Appl. Crystallogr. 24: 946-956.
Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F., and Richmond, T.J. 1997. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389: 251-260.[CrossRef][Medline]
Merritt, E.A. and Bacon, D.J. 1997. Raster3D: Photorealistic molecular graphics. Method. Enzymol. 277: 505-524.[Medline]
Messmer, S.,
Franke, A., and Paro, R. 1992. Analysis of the functional role of
the Polycomb chromo domain in Drosophila melanogaster.
Genes & Dev. 6:
1241-1254.
Muller, J., Hart, C.M., Francis, N.J., Vargas, M.L., Sengupta, A., Wild, B., Miller, E.L., O'Connor, M.B., Kingston, R.E., and Simon, J.A. 2002. Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111: 197-208.[CrossRef][Medline]
Nakayama, J.,
Rice, J.C., Strahl, B.D., Allis, C.D., and Grewal, S.I. 2001.
Role of histone H3 lysine 9 methylation in epigenetic control of
heterochromatin assembly. Science
292:
110-113.
Navaza, J. 2001. Implementation of molecular replacement in AMoRe. Acta Crystallogr. D 57: 1367-1372.[CrossRef][Medline]
Nicholls, A., Sharp, K.A., and Honig, B. 1991. Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 11: 281-296.[CrossRef][Medline]
Nielsen, P.R., Nietlispach, D., Mott, H.R., Callaghan, J., Bannister, A., Kouzarides, T., Murzin, A.G., Murzina, N.V., and Laue, E.D. 2002. Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9. Nature 416: 103-107.[CrossRef][Medline]
Otwinowski, Z. and Minor, W. 1997. Processing of X-ray diffraction data collected in oscillation mode. Method. Enzymol. 276: 307-326.
Paro, R. and
Hogness, D.S. 1991. The Polycomb protein shares a homologous
domain with a heterochromatin-associated protein of Drosophila.
Proc. Natl. Acad. Sci.
88:
263-267.
Perrakis, A., Morris, R., and Lamzin, V.S. 1999. Automated protein model building combined with iterative structure refinement. Nat. Struct. Biol. 6: 458-463.[CrossRef][Medline]
Platero, J.S., Hartnett, T., and Eissenberg, J.C. 1995. Functional analysis of the chromo domain of HP1. EMBO J. 14: 3977-3986.[Medline]
Plath, K., Fang,
J., Mlynarczyk-Evans, S.K., Cao, R., Worringer, K.A., Wang, H., de la Cruz,
C.C., Otte, A.P., Panning, B., and Zhang, Y. 2003. Role of
histone H3 lysine 27 methylation in X inactivation.
Science 300:
131-135.
Powers, J.A. and
Eissenberg, J.C. 1993. Overlapping domains of the
heterochromatin-associated protein HP1 mediate nuclear localization and
heterochromatin binding. J. Cell Biol.
120:
291-299.
Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B.D., Sun, Z.W., Schmid, M., Opravil, S., Mechtler, K., Ponting, C.P., Allis, C.D., et al. 2000. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406: 593-599.[CrossRef][Medline]
Silva, J., Mak, W., Zvetkova, I., Appanah, R., Nesterova, T.B., Webster, Z., Peters, A.H., Jenuwein, T., Otte, A.P., and Brockdorff, N. 2003. Establishment of histone H3 methylation on the inactive X chromosome requires transient recruitment of eed-enx1 polycomb group complexes. Dev. Cell 4: 481-495.[CrossRef][Medline]
Strahl, B.D. and Allis, C.D. 2000. The language of covalent histone modifications. Nature 403: 41-45.[CrossRef][Medline]
Turner, B.M. 2000. Histone acetylation and an epigenetic code. Bioessays 22: 836-845.[CrossRef][Medline]
Zhang, Y. and
Reinberg, D. 2001. Transcription regulation by histone
methylation: Interplay between different covalent modifications of the core
histone tails. Genes & Dev.
15:
2343-2360.
Zink, B. and Paro, R. 1989. In vivo binding pattern of a trans-regulator of homoeotic genes in Drosophila melanogaster. Nature 337: 468-471.[CrossRef][Medline]
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. K. Sims and J. C. Rice PR-Set7 Establishes a Repressive trans-Tail Histone Code That Regulates Differentiation Mol. Cell. Biol., July 15, 2008; 28(14): 4459 - 4468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Fischle, H. Franz, S. A. Jacobs, C. D. Allis, and S. Khorasanizadeh Specificity of the Chromodomain Y Chromosome Family of Chromodomains for Lysine-methylated ARK(S/T) Motifs J. Biol. Chem., July 11, 2008; 283(28): 19626 - 19635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamashita, M. Kuwahara, A. Suzuki, K. Hirahara, R. Shinnaksu, H. Hosokawa, A. Hasegawa, S. Motohashi, A. Iwama, and T. Nakayama Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene J. Exp. Med., May 12, 2008; 205(5): 1109 - 1120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sarma, R. Margueron, A. Ivanov, V. Pirrotta, and D. Reinberg Ezh2 Requires PHF1 To Efficiently Catalyze H3 Lysine 27 Trimethylation In Vivo Mol. Cell. Biol., April 15, 2008; 28(8): 2718 - 2731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Endoh, T. A. Endo, T. Endoh, Y.-i. Fujimura, O. Ohara, T. Toyoda, A. P. Otte, M. Okano, N. Brockdorff, M. Vidal, et al. Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity Development, April 15, 2008; 135(8): 1513 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Cao, H. Wang, J. He, H. Erdjument-Bromage, P. Tempst, and Y. Zhang Role of hPHF1 in H3K27 Methylation and Hox Gene Silencing Mol. Cell. Biol., March 1, 2008; 28(5): 1862 - 1872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Gao, Y. Hou, H. Ebina, H. L. Levin, and D. F. Voytas Chromodomains direct integration of retrotransposons to heterochromatin Genome Res., March 1, 2008; 18(3): 359 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Savla, J. Benes, J. Zhang, and R. S. Jones Recruitment of Drosophila Polycomb-group proteins by Polycomblike, a component of a novel protein complex in larvae Development, March 1, 2008; 135(5): 813 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-C. Yuan, X. Zhao, L. Florens, S. K. Swanson, M. P. Washburn, and N. Hernandez CHD8 Associates with Human Staf and Contributes to Efficient U6 RNA Polymerase III Transcription Mol. Cell. Biol., December 15, 2007; 27(24): 8729 - 8738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Holbert, T. Sikorski, J. Carten, D. Snowflack, S. Hodawadekar, and R. Marmorstein The Human Monocytic Leukemia Zinc Finger Histone Acetyltransferase Domain Contains DNA-binding Activity Implicated in Chromatin Targeting J. Biol. Chem., December 14, 2007; 282(50): 36603 - 36613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ramon-Maiques, A. J. Kuo, D. Carney, A. G. W. Matthews, M. A. Oettinger, O. Gozani, and W. Yang The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2 PNAS, November 27, 2007; 104(48): 18993 - 18998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, S. D. Taverna, T. L. Muratore, J. Shabanowitz, D. F. Hunt, and C. D. Allis RNAi-dependent H3K27 methylation is required for heterochromatin formation and DNA elimination in Tetrahymena Genes & Dev., June 15, 2007; 21(12): 1530 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sakamoto, S. Watanabe, T. Ichimura, M. Kawasuji, H. Koseki, H. Baba, and M. Nakao Overlapping Roles of the Methylated DNA-binding Protein MBD1 and Polycomb Group Proteins in Transcriptional Repression of HOXA Genes and Heterochromatin Foci Formation J. Biol. Chem., June 1, 2007; 282(22): 16391 - 16400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Tie, C. A. Stratton, R. L. Kurzhals, and P. J. Harte The N Terminus of Drosophila ESC Binds Directly to Histone H3 and Is Required for E(Z)-Dependent Trimethylation of H3 Lysine 27 Mol. Cell. Biol., March 15, 2007; 27(6): 2014 - 2026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zhang, J. Du, B. Sun, X. Dong, G. Xu, J. Zhou, Q. Huang, Q. Liu, Q. Hao, and J. Ding Structure of human MRG15 chromo domain and its binding to Lys36-methylated histone H3 Nucleic Acids Res., December 2, 2006; 34(22): 6621 - 6628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Qi, H. Jin, T. Lilja, and M. Mannervik Drosophila Reptin and Other TIP60 Complex Components Promote Generation of Silent Chromatin Genetics, September 1, 2006; 174(1): 241 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Papp and J. Muller Histone trimethylation and the maintenance of transcriptional ONand OFF states by trxG and PcG proteins Genes & Dev., August 1, 2006; 20(15): 2041 - 2054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ueda, M. Tachibana, T. Ikura, and Y. Shinkai Zinc Finger Protein Wiz Links G9a/GLP Histone Methyltransferases to the Co-repressor Molecule CtBP J. Biol. Chem., July 21, 2006; 281(29): 20120 - 20128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Heard and C. M. Disteche Dosage compensation in mammals: fine-tuning the expression of the X chromosome Genes & Dev., July 15, 2006; 20(14): 1848 - 1867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Huang, J. Fang, M. T. Bedford, Y. Zhang, and R.-M. Xu Recognition of Histone H3 Lysine-4 Methylation by the Double Tudor Domain of JMJD2A Science, May 5, 2006; 312(5774): 748 - 751. [Abstract] [Full Text] [PDF]
|
|
contour level with
a 3.0
are human HP1 homologs with the SWISS-PROT
accession codes P45973
