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Abstract
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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