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Structural protein
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PDB id
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1pdq
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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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nucleus
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2 terms
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Biological process
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chromatin assembly or disassembly
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1 term
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Biochemical function
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chromatin binding
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1 term
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DOI no:
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Genes Dev
17:1870-1881
(2003)
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PubMed id:
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Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains.
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W.Fischle,
Y.Wang,
S.A.Jacobs,
Y.Kim,
C.D.Allis,
S.Khorasanizadeh.
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ABSTRACT
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On the histone H3 tail, Lys 9 and Lys 27 are both methylation sites associated
with epigenetic repression, and reside within a highly related sequence motif
ARKS. Here we show that the chromodomain proteins Polycomb (Pc) and HP1
(heterochromatin protein 1) are highly discriminatory for binding to these sites
in vivo and in vitro. In Drosophila S2 cells, and on polytene chromosomes,
methyl-Lys 27 and Pc are both excluded from areas that are enriched in
methyl-Lys 9 and HP1. Swapping of the chromodomain regions of Pc and HP1 is
sufficient for switching the nuclear localization patterns of these factors,
indicating a role for their chromodomains in both target site binding and
discrimination. To better understand the molecular basis for the selection of
methyl-lysine binding sites, we solved the 1.8 A structure of the Pc
chromodomain in complex with a H3 peptide bearing trimethyl-Lys 27, and compared
it with our previously determined structure of the HP1 chromodomain in complex
with a H3 peptide bearing trimethyl-Lys 9. The Pc chromodomain distinguishes its
methylation target on the H3 tail via an extended recognition groove that binds
five additional residues preceding the ARKS motif.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
|
|
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|
|
|
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and
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| |
Chembiochem, 12,
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and
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The SUUR protein is involved in binding of SU(VAR)3-9 and methylation of H3K9 and H3K27 in chromosomes of Drosophila melanogaster.
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| |
Chromosome Res, 19,
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M.Gerstung,
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| |
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| |
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and
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(2011).
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and
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(2011).
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| |
J Biol Chem, 286,
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|
|
|
PDB codes:
|
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|
|
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|
|
N.Koester-Eiserfunke,
and
W.Fischle
(2011).
H3K9me2/3 binding of the MBT domain protein LIN-61 is essential for Caenorhabditis elegans vulva development.
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| |
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| |
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| |
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Bioessays, 33,
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| |
Cell Mol Life Sci, 68,
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H.M.Chen,
and
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| |
Cancer Invest, 29,
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A.Jones,
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| |
Protein Cell, 1,
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and
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Chromatin higher-order structure and dynamics.
|
| |
Cold Spring Harb Perspect Biol, 2,
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|
|
|
C.S.Beshara,
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K.D.Daze,
B.J.Lilgert,
and
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A simple calixarene recognizes post-translationally methylated lysine.
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| |
Chembiochem, 11,
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C.Xu,
C.Bian,
W.Yang,
M.Galka,
H.Ouyang,
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W.Qiu,
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P.Pan,
S.S.Li,
H.Wang,
and
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(2010).
Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2).
|
| |
Proc Natl Acad Sci U S A, 107,
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|
|
|
PDB codes:
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|
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D.P.Nguyen,
M.M.Garcia Alai,
S.Virdee,
and
J.W.Chin
(2010).
Genetically directing É›-N, N-dimethyl-L-lysine in recombinant histones.
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S.Forcob,
W.J.Chang,
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The evolutionary history of histone H3 suggests a deep eukaryotic root of chromatin modifying mechanisms.
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and
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| |
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and
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(2010).
Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a.
|
| |
Mol Cell, 38,
662-674.
|
|
|
PDB code:
|
|
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|
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|
|
L.E.Surface,
S.R.Thornton,
and
L.A.Boyer
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Polycomb group proteins set the stage for early lineage commitment.
|
| |
Cell Stem Cell, 7,
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E.L.Miller,
C.S.Ketel,
D.R.Mallin,
and
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(2010).
Comparative analysis of chromatin binding by Sex Comb on Midleg (SCM) and other polycomb group repressors at a Drosophila Hox gene.
|
| |
Mol Cell Biol, 30,
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|
|
|
|
|
|
|
M.Billur,
H.D.Bartunik,
and
P.B.Singh
(2010).
The essential function of HP1 beta: a case of the tail wagging the dog?
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| |
Trends Biochem Sci, 35,
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|
|
|
|
|
M.Leeb,
D.Pasini,
M.Novatchkova,
M.Jaritz,
K.Helin,
and
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(2010).
Polycomb complexes act redundantly to repress genomic repeats and genes.
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| |
Genes Dev, 24,
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|
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|
|
|
|
|
Q.Ding,
and
D.M.MacAlpine
(2010).
Preferential re-replication of Drosophila heterochromatin in the absence of geminin.
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| |
PLoS Genet, 6,
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|
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Q.Zhu,
and
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(2010).
Histone modifications: crucial elements for damage response and chromatin restoration.
|
| |
J Cell Physiol, 223,
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and
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Exp Gerontol, 45,
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S.Kubicek,
S.L.Schreiber,
and
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(2010).
Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres.
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| |
Nat Struct Mol Biol, 17,
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|
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|
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S.Kaveti,
R.W.Desnoyer,
B.Willard,
M.Kinter,
and
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(2010).
AT1 receptor induced alterations in histone H2A reveal novel insights into GPCR control of chromatin remodeling.
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PLoS One, 5,
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P.J.Hart,
E.M.Lafer,
B.Demeler,
A.P.Hinck,
D.G.McEwen,
and
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(2010).
Polycomb group targeting through different binding partners of RING1B C-terminal domain.
|
| |
Structure, 18,
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|
|
|
PDB codes:
|
|
|
|
|
|
|
|
S.Balasubramanian,
G.Adhikary,
and
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(2010).
The Bmi-1 polycomb protein antagonizes the (-)-epigallocatechin-3-gallate-dependent suppression of skin cancer cell survival.
|
| |
Carcinogenesis, 31,
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|
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|
S.Falk,
S.Ravaud,
J.Koch,
and
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(2010).
The C terminus of the Alb3 membrane insertase recruits cpSRP43 to the thylakoid membrane.
|
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J Biol Chem, 285,
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T.K.Barth,
and
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SUMO-specific protease 2 is essential for suppression of polycomb group protein-mediated gene silencing during embryonic development.
|
| |
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X.Lu,
and
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(2010).
Chromatin assembly on herpes simplex virus genomes during lytic infection.
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and
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E.V.Dementyeva,
and
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Mosaic heterochromatin of the inactive X chromosome in vole Microtus rossiaemeridionalis.
|
| |
Mamm Genome, 20,
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and
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| |
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J.Jackson,
M.D.Simon,
B.Fleharty,
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and
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(2009).
Histone H3 lysine 36 dimethylation (H3K36me2) is sufficient to recruit the Rpd3s histone deacetylase complex and to repress spurious transcription.
|
| |
J Biol Chem, 284,
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|
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C.A.Musselman,
R.E.Mansfield,
A.L.Garske,
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J.P.Mackay,
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(2009).
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|
| |
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and
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(2009).
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| |
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|
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(2009).
ATRX marks the inactive X chromosome (Xi) in somatic cells and during imprinted X chromosome inactivation in trophoblast stem cells.
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| |
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(2009).
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| |
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(2009).
Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.
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| |
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(2009).
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| |
PLoS ONE, 4,
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|
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M.Serrano,
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(2009).
Polycomb mediated epigenetic silencing and replication timing at the INK4a/ARF locus during senescence.
|
| |
PLoS One, 4,
e5622.
|
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A.J.Saurin,
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N.Mossadegh,
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A.P.Otte,
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(2009).
The PRC1 Polycomb group complex interacts with PLZF/RARA to mediate leukemic transformation.
|
| |
Genes Dev, 23,
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|
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|
H.Franz,
K.Mosch,
S.Soeroes,
H.Urlaub,
and
W.Fischle
(2009).
Multimerization and H3K9me3 binding are required for CDYL1b heterochromatin association.
|
| |
J Biol Chem, 284,
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|
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E.Heard,
and
H.G.Stunnenberg
(2009).
High-resolution analysis of epigenetic changes associated with X inactivation.
|
| |
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J.A.Rosenfeld,
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