Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1

Musselman, Catherine A.; Avvakumov, Nikita; Watanabe, Reiko; Abraham, Christopher G.; Lalonde, Marie-Eve; Zhang, Hong; Allen, Chris; Roy, Siddhartha; Nuñez, James K.; Nickoloff, Jac A.; Kulesza, Caroline; Yasui, Akira; Côté, Jacques; Kutateladze, Tatiana G.

doi:10.1038/nsmb.2435

Cited by 174 publications

(203 citation statements)

References 48 publications

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“…3a, b), similar to the results from isolated Tudor domains 4,6,7,11,15,16 , suggesting that the presence of the other domains does not interfere with the histone binding preference. In addition, we confirmed that the Tudor domains rather than the PHD1/2 fingers are responsible for the above recognition, as mutation of an aromatic-cage residue in the Tudor domain (Y47A for PHF1, Y62A for MTF2) led to a complete loss in binding affinity (Extended Data Table 2).…”

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confidence: 81%

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Polycomb-like proteins link the PRC2 complex to CpG islands

Liefke

Jiang

et al. 2017

Nature

247

314

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The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression1,2 and plays essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like proteins (PCLs), including PHF1, MTF2 and PHF19, are PRC2 associated factors that form sub-complexes with PRC2 core components3, and have been proposed to modulate PRC2’s enzymatic activity or its recruitment to specific genomic loci4–13. Mammalian PRC2 binding sites are enriched in CG content, which correlate with CpG islands that display a low level of DNA methylation14. However, the mechanism of PRC2 recruitment to CpG islands is not fully understood. In this study, we solved the crystal structures of the N-terminal domains of PHF1 and MTF2 with bound CpG-containing DNAs in the presence of H3K36me3-containing histone peptides. We found that the extended homologous (EH) regions of both proteins fold into a winged-helix structure, which specifically binds to the unmethylated CpG motif but in a manner completely different from the canonical winged-helix motif-DNA recognition. We further showed that the PCL EH domains are required for efficient recruitment of PRC2 to CpG island-containing promoters in mouse embryonic cells. Our research provides the first direct evidence demonstrating that PCLs are critical for PRC2 recruitment to CpG islands, thereby further clarifying their roles in transcriptional regulation in vivo.

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confidence: 81%

“…1a). Currently, only the structures of the isolated Tudor domains of PCLs have been solved, which bind preferentially to histone H3 trimethylated at lysine 36 (H3K36me3) 4,6,7,11,15,16 . We solved the crystal structure of the PHF1 Tudor-PHD1-PHD2-EH cassette at 1.9 Å resolution (Extended Data Table 1).…”

mentioning

confidence: 99%

Polycomb-like proteins link the PRC2 complex to CpG islands

Liefke

Jiang

et al. 2017

Nature

247

314

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“…In addition, one of the alternative complex subunits, PHF1/ Pcl, can also modulate the PRC2 complex activity (Cao et al 2008;Sarma et al 2008). Its N-terminal Tudor domain can recognize H3K36me3-containing chromatin, either inhibiting Ezh2 from methylating H3K27 or promoting its spreading and silencing on embryonic stem cell genes (Abed and Jones 2012;Musselman et al 2012a;Cai et al 2013). The Set1 methyltransferase is a member of the COMPASS complex (MLL1/Set1a/Set1b complexes in humans).…”

Section: Selection Of Specific Ptm-carrying Nucleosomes By Modifier Ementioning

confidence: 99%

Histone target selection within chromatin: an exemplary case of teamwork

2014

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Histone modifiers like acetyltransferases, methyltransferases, and demethylases are critical regulators of most DNA-based nuclear processes, de facto controlling cell cycle progression and cell fate. These enzymes perform very precise post-translational modifications on specific histone residues, which in turn are recognized by different effector modules/proteins. We now have a better understanding of how these enzymes exhibit such specificity. As they often reside in multisubunit complexes, they use associated factors to target their substrates within chromatin structure and select specific histone mark-bearing nucleosomes. In this review, we cover the current understanding of how histone modifiers select their histone targets. We also explain how different experimental approaches can lead to conflicting results about the histone specificity and function of these enzymes.

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“…The mammalian Pcl homolog PCL2 (MTF2) was shown to associate with PRC2 and to modulate transcription of selected PcG target genes, suggesting that PCL2 is involved in the recruitment of the PRC2 to chromatin Walker et al 2010). PCL1 (PHF1) and PCL3 (PHF19) are two other mammalian homologs of Pcl that were shown to recruit PRC2 to chromatin through interactions with the active chromatin mark H3K36me3 (Ballaré et al 2012;Brien et al 2012;Musselman et al 2012). JARID2, which plays an essential role in embryonic development, interacts with PRC2, regulates its activity, and facilitates its recruitment to chromatin (Peng et al 2009;Shen et al 2009;Landeira et al 2010;Li et al 2010;Pasini et al 2010) (for review, see Herz and Shilatifard 2010).…”

Section: Introductionmentioning

confidence: 99%

The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2

Davidovich

Cech

2015

RNA

253

218

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Polycomb repressive complex-2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Among chromatin modifying factors shown to be recruited and regulated by long noncoding RNAs (lncRNAs), PRC2 is one of the most studied. Mammalian PRC2 binds thousands of RNAs in vivo, and it is becoming a model system for the recruitment of chromatin modifying factors by RNA. Yet, well-defined PRC2-binding motifs within target RNAs have been elusive. From the protein side, PRC2 RNA-binding subunits contain no known RNA-binding domains, complicating functional studies. Here we provide a critical review of existing models for the recruitment of PRC2 to chromatin by RNAs. This discussion may also serve researchers who are studying the recruitment of other chromatin modifiers by lncRNAs.

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Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1

Cited by 174 publications

References 48 publications

Polycomb-like proteins link the PRC2 complex to CpG islands

Polycomb-like proteins link the PRC2 complex to CpG islands

Histone target selection within chromatin: an exemplary case of teamwork

The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2

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