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PDBsum entry 2jmj
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Protein binding
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PDB id
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2jmj
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References listed in PDB file
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Key reference
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Title
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Yng1 phd finger binding to h3 trimethylated at k4 promotes nua3 hat activity at k14 of h3 and transcription at a subset of targeted orfs.
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Authors
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S.D.Taverna,
S.Ilin,
R.S.Rogers,
J.C.Tanny,
H.Lavender,
H.Li,
L.Baker,
J.Boyle,
L.P.Blair,
B.T.Chait,
D.J.Patel,
J.D.Aitchison,
A.J.Tackett,
C.D.Allis.
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Ref.
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Mol Cell, 2006,
24,
785-796.
[DOI no: ]
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PubMed id
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Abstract
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Posttranslational histone modifications participate in modulating the structure
and function of chromatin. Promoters of transcribed genes are enriched with K4
trimethylation and hyperacetylation on the N-terminal tail of histone H3.
Recently, PHD finger proteins, like Yng1 in the NuA3 HAT complex, were shown to
interact with H3K4me3, indicating a biochemical link between K4 methylation and
hyperacetylation. By using a combination of mass spectrometry, biochemistry, and
NMR, we detail the Yng1 PHD-H3K4me3 interaction and the importance of
NuA3-dependent acetylation at K14. Furthermore, genome-wide ChIP-Chip analysis
demonstrates colocalization of Yng1 and H3K4me3 in vivo. Disrupting the K4me3
binding of Yng1 altered K14ac and transcription at certain genes, thereby
demonstrating direct in vivo evidence of sequential trimethyl binding,
acetyltransferase activity, and gene regulation by NuA3. Our data support a
general mechanism of transcriptional control through which histone acetylation
upstream of gene activation is promoted partially through availability of
H3K4me3, "read" by binding modules in select subunits.
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Figure 4.
Figure 4. NMR Structure of the Yng1 PHD Interaction with
Trimethylated H3 K4
NMR-derived structure of the PHD finger
(152–212) in the free form. For clarity, residues 152–154
and 208–212 in the unstructured regions were omitted.
(A)
Backbone superposition of 20 energy-minimized structures of the
PHD finger.
(B) Aromatically rich surface that shows
extensive chemical shift changes upon peptide binding (Y157 and
W180).
(C) Backbone superposition of 20 energy-minimized
structures of the PHD finger in complex with H3[1–9]K4me3
peptide.
(D) Aromatically rich surface that shows extensive
interactions with trimethylated lysine K4 (Y157 and W180).
(E) Surface representation of the YNG1 PHD complex with
H3[1–9]K4me3 peptide. Surface residues that undergo the
largest chemical shift upon binding are highlighted in pink.
(F) An ensemble of 20 structures with side chains involved
in complex formation colored in purple (D172 and E179 for H3 R2,
Y157 and W180 for H3K4).
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Figure 7.
Figure 7. Model for H3K4me3-Directed Activity of NuA3
(A) Set1, the H3K4 HMT, is recruited to promoter-proximal
nucleosomes at the ORF to be activated, resulting in H3K4me3.
(B) NuA3 is targeted to and/or retained at sites of H3K4me3
through interactions with the PHD finger of Yng1, promoting
H3K14ac via the Sas3 HAT, positively regulating downstream
transcription events.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2006,
24,
785-796)
copyright 2006.
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