Molecular recognition of histone lysine methylation by the Polycomb group repressor dSfmbt

European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France.
The EMBO Journal (Impact Factor: 10.43). 07/2009; 28(13):1965-77. DOI: 10.1038/emboj.2009.147
Source: PubMed


Polycomb group (PcG) proteins repress transcription by modifying chromatin structure in target genes. dSfmbt is a subunit of the Drosophila melanogaster PcG protein complex PhoRC and contains four malignant brain tumour (MBT) repeats involved in the recognition of various mono- and dimethylated histone peptides. Here, we present the crystal structure of the four-MBT-repeat domain of dSfmbt in complex with a mono-methylated histone H4 peptide. Only a single histone peptide binds to the four-MBT-repeat domain. Mutational analyses show high-affinity binding with low peptide sequence selectivity through combinatorial interaction of the methyl-lysine with an aromatic cage and positively charged flanking residues with the surrounding negatively charged surface of the fourth MBT repeat. dSfmbt directly interacts with the PcG protein Scm, a related MBT-repeat protein with similar methyl-lysine binding activity. dSfmbt and Scm co-occupy Polycomb response elements of target genes in Drosophila and they strongly synergize in the repression of these target genes, suggesting that the combined action of these two MBT proteins is crucial for Polycomb silencing.

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    • "It is found that the direct interaction among D. melanogaster PcG proteins, Scm-related protein containing four mbt domains (dSfmbt) and Sex comb on midleg (Scm) is mediated by the zf-FCS domains present in both proteins. Both these proteins interact and cooperate synergistically for mediating target gene repression [18]. All these reports shows that zf-FCS is a structurally diverse family which accommodate both nucleic-protein and protein-protein interaction zinc fingers. "
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    PLoS ONE 06/2014; 9(6):e99074. DOI:10.1371/journal.pone.0099074 · 3.23 Impact Factor
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    • "Methylated histone tails are recognized by chromatin-reading modules such as Chromo, Tudor, PWWP and MBT (malignant brain tumor) domains, together designated as the ‘Royal family’ of chromatin binding domains (1). MBT-domain proteins contain arrays of two (2,3), three (4–6) or four (7–9) MBT domains that form an interlocked substructure that bind specifically to mono- and dimethylated lysine residues on histone tails. In humans, the family of MBT-domain proteins comprises nine members, which can be almost invariably linked to one of the three Drosophila MBT-domain proteins L(3)mbt, Scm and Sfmbt. "
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    • "Therefore, Sfmbt is an important partner of Pho in recruiting PRC2 and PRC1 complexes to the target gene. Sfmbt protein contains several functional domains including four MBT repeats and one SAM, which can interact with other Polycomb proteins such as Pho and Scm [20]. Scm protein had strikingly similar domain architecture with Sfmbt and was considered as a PRC1 component [8]. "
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