Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27.

By J. Min, Yi Zhang, R. Xu. Genes & Development, 2003

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The chromodomain of Drosophila Polycomb protein is essential for maintaining the silencing state of homeotic genes during development. Recent studies suggest that Polycomb mediates the assembly of repressive higher-order chromatin structures in conjunction with the methylation of Lys 27 of histone H3 by a Polycomb group repressor complex. A similar mechanism in heterochromatin assembly is mediated by HP1, a chromodomain protein that binds to histone H3 methylated at Lys 9. To understand the molecular mechanism of the methyl-Lys 27 histone code recognition, we have determined a 1.4-A-resolution structure of the chromodomain of Polycomb in complex with a histone H3 peptide trimethylated at Lys 27. The structure reveals a conserved mode of methyl-lysine binding and identifies Polycomb-specific interactions with histone H3. The structure also reveals a dPC dimer in the crystal lattice that is mediated by residues specifically conserved in the Polycomb family of chromodomains. The dimerization of dPC can effectively account for the histone-binding specificity and provides new mechanistic insights into the function of Polycomb. We propose that self-association is functionally important for Polycomb.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/06d6cb93ca0b73a3a794648a391536da7d8057d6

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Citations in the corpus

Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. (2005, background): “These data are consistent with the notion that H3-K27 methylation provides a binding site for Pc (Fischle et al., 2003; Min et al., 2003) and thus contributes to PRC1 recruitment and H2A ubiquitylation.”
Molecular Interplay of the Non-coding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a (2010, neutral): “The structure is similar to that of other chromodomains bound to H3 peptides including mouse HP1bCD/H3K9me2 and 668 Molecular Cell 38, 662–674, June 11, 2010 ª2010 Elsevier Inc. Drosophila PcCD/H3K27me3 (Fischle et al., 2003; Jacobs and Khorasanizadeh, 2002; Min et al., 2003; Nielsen et al., 2002).”
JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. (2006, methodology): “Plasmids encoding GST-SET7, GST-SET8, GST-hDOT1L (1–416),and components of the EZH2 complex have been previously described (Cao and Zhang, 2004; Min et al., 2003; Wang et al., 2001a, 2001b).”
Bmi1 is essential in Twist1-induced epithelial–mesenchymal transition (2010, background): “PRC1 recognizes trimethylated H3K27 (H3K27me3) and maintains the repression of target gene”
RNA meets chromatin. (2005, background): “Moreover, atomic structures of both protein–peptide complexes have been determined, which suggest a common binding fold using two features: (1) The H3 peptide itself binds by inserting itself as a missing “rung” in a -stranded core architecture; and (2) the positively charged methyl ammonium ion is ”
PCGF Homologs, CBX Proteins, and RYBP Define Functionally Distinct PRC1 Family Complexes (2012, background): “…(Saurin et al., 2001; Shao et al., 1999) contains Polycomb (Pc), a chromodomain-containing protein that binds to H3K27me3 (Fischle et al., 2003; Min et al., 2003); dRing, the enzyme responsible for H2A ubiquitination (Wang et al., 2004); Posterior sex combs (Psc), which is responsible for…”
SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. (2004, background): “…spatial patterns of homeotic box (Hox) acidsof H3precedinglysine 27contributeto thespecific gene expression, which are established early in embry-recognition of the methylated lysine 27 by Pc chromo onic development by transiently expressed segmenta-domain (Fischle et al., 2003; Min et al., 2003).”
The nucleosome: from genomic organization to genomic regulation. (2004, methodology): “A channel is used to accommodate the target lysine 9 sidestages (Fischle et al., 2003a; Min et al., 2003b).”