Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines

Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recogni...

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Bibliographic Details
Published in:Molecular cell 2017-03, Vol.65 (6), p.1056-1067.e5
Main Authors: Wang, Xueyin, Goodrich, Karen J., Gooding, Anne R., Naeem, Haroon, Archer, Stuart, Paucek, Richard D., Youmans, Daniel T., Cech, Thomas R., Davidovich, Chen
Format: Article
Language:English
Subjects:
Binding Sites
Chromatin - chemistry
Chromatin - enzymology
Chromatin - genetics
Enhancer of Zeste Homolog 2 Protein - genetics
Enhancer of Zeste Homolog 2 Protein - metabolism
G-quadruplex
Gene Expression Regulation
Guanine - metabolism
HEK293 Cells
Humans
motif
Nucleic Acid Conformation
Nucleosomes - chemistry
Nucleosomes - enzymology
Nucleosomes - genetics
Nucleotide Motifs
Polycomb repressive complex 2
Polycomb Repressive Complex 2 - genetics
Polycomb Repressive Complex 2 - metabolism
PRC2
promiscuous RNA binding
Protein Binding
RNA - chemistry
RNA - genetics
RNA - metabolism
RNA binding specificity
Structure-Activity Relationship
Transfection
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Summary:Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recognizes G > C,U ≫ A in single-stranded RNA and has a high affinity for folded guanine quadruplex (G4) structures but little binding to duplex RNAs. Importantly, G-tract motifs are significantly enriched among PRC2-binding transcripts in vivo. DNA sequences coding for PRC2-binding RNA motifs are enriched at PRC2-binding sites on chromatin and H3K27me3-modified nucleosomes. Collectively, the abundance of PRC2-binding RNA motifs rationalizes the promiscuous RNA binding of PRC2, and their enrichment at Polycomb target genes provides a means for RNA-mediated regulation. [Display omitted] •PRC2 binds to an RNA motif composed of short repeats of consecutive guanines•The natural abundance of this motif explains promiscuous RNA binding by PRC2•PRC2 has a high affinity for G-quadruplex RNA and little affinity for duplex RNA•Enrichment of the motif at PRC2 target genes provides a means for regulation in cis Wang et al. discovered how the epigenetic modifier PRC2 recognizes RNA. The PRC2-binding motif includes multiple tracts of consecutive guanines, and its abundance within transcripts rationalizes promiscuous RNA binding by PRC2 in vivo. The motif is enriched at Polycomb target genes and provides a means for RNA-mediated regulation of PRC2 in cis.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2017.02.003