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PDBsum entry 2kvm
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Transcription
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PDB id
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2kvm
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References listed in PDB file
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Key reference
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Title
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Molecular interplay of the noncoding RNA anril and methylated histone h3 lysine 27 by polycomb cbx7 in transcriptional silencing of ink4a.
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Authors
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K.L.Yap,
S.Li,
A.M.Muñoz-Cabello,
S.Raguz,
L.Zeng,
S.Mujtaba,
J.Gil,
M.J.Walsh,
M.M.Zhou.
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Ref.
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Mol Cell, 2010,
38,
662-674.
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PubMed id
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Abstract
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Expression of the INK4b/ARF/INK4a tumor suppressor locus in normal and cancerous
cell growth is controlled by methylation of histone H3 at lysine 27 (H3K27me) as
directed by the Polycomb group proteins. The antisense noncoding RNA ANRIL of
the INK4b/ARF/INK4a locus is also important for expression of the protein-coding
genes in cis, but its mechanism has remained elusive. Here we report that
chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and
both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. In
concert with H3K27me recognition, binding to RNA contributes to CBX7 function,
and disruption of either interaction impacts the ability of CBX7 to repress the
INK4b/ARF/INK4a locus and control senescence. Structure-guided analysis reveals
the molecular interplay between noncoding RNA and H3K27me as mediated by the
conserved chromodomain. Our study suggests a mechanism by which noncoding RNA
participates directly in epigenetic transcriptional repression.
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