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| | ==Ternary complex of PHF1, a DNA duplex and a histone peptide== | | ==Ternary complex of PHF1, a DNA duplex and a histone peptide== |
| - | <StructureSection load='5xfq' size='340' side='right' caption='[[5xfq]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='5xfq' size='340' side='right'caption='[[5xfq]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xfq]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XFQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XFQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xfq]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XFQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XFQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5xfn|5xfn]], [[5xfo|5xfo]], [[5xfp|5xfp]], [[5xfr|5xfr]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5xfq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xfq OCA], [https://pdbe.org/5xfq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xfq RCSB], [https://www.ebi.ac.uk/pdbsum/5xfq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xfq ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xfq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xfq OCA], [http://pdbe.org/5xfq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xfq RCSB], [http://www.ebi.ac.uk/pdbsum/5xfq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xfq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PHF1_MOUSE PHF1_MOUSE]] Polycomb group (PcG) that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex. Involved in DNA damage response and is recruited at double-strand breaks (DSBs). Acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting the PRC2 complex: it is however unclear whether recruitment of the PRC2 complex to H3K36me3 leads to enhance or inhibit H3K27me3 methylation mediated by the PRC2 complex. According to some reports, PRC2 recruitment by PHF1 promotes H3K27me3 and subsequent gene silencing by inducing spreading of PRC2 and H3K27me3 into H3K36me3 loci (PubMed:18086877). According to other reports, PHF1 recruits the PRC2 complex at double-strand breaks (DSBs) and inhibits the activity of PRC2. Regulates p53/TP53 stability and prolonges its turnover: may act by specifically binding to a methylated from of p53/TP53.<ref>PMID:18086877</ref> | + | [https://www.uniprot.org/uniprot/PHF1_MOUSE PHF1_MOUSE] Polycomb group (PcG) that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex. Involved in DNA damage response and is recruited at double-strand breaks (DSBs). Acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting the PRC2 complex: it is however unclear whether recruitment of the PRC2 complex to H3K36me3 leads to enhance or inhibit H3K27me3 methylation mediated by the PRC2 complex. According to some reports, PRC2 recruitment by PHF1 promotes H3K27me3 and subsequent gene silencing by inducing spreading of PRC2 and H3K27me3 into H3K36me3 loci (PubMed:18086877). According to other reports, PHF1 recruits the PRC2 complex at double-strand breaks (DSBs) and inhibits the activity of PRC2. Regulates p53/TP53 stability and prolonges its turnover: may act by specifically binding to a methylated from of p53/TP53.<ref>PMID:18086877</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Li, H]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Wang, Z]] | + | [[Category: Large Structures]] |
| - | [[Category: Dna]] | + | [[Category: Mus musculus]] |
| - | [[Category: Histone]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Pcl1]] | + | [[Category: Li H]] |
| - | [[Category: Phf1]] | + | [[Category: Wang Z]] |
| - | [[Category: Transcription-dna complex]]
| + | |
| Structural highlights
Function
PHF1_MOUSE Polycomb group (PcG) that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex. Involved in DNA damage response and is recruited at double-strand breaks (DSBs). Acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting the PRC2 complex: it is however unclear whether recruitment of the PRC2 complex to H3K36me3 leads to enhance or inhibit H3K27me3 methylation mediated by the PRC2 complex. According to some reports, PRC2 recruitment by PHF1 promotes H3K27me3 and subsequent gene silencing by inducing spreading of PRC2 and H3K27me3 into H3K36me3 loci (PubMed:18086877). According to other reports, PHF1 recruits the PRC2 complex at double-strand breaks (DSBs) and inhibits the activity of PRC2. Regulates p53/TP53 stability and prolonges its turnover: may act by specifically binding to a methylated from of p53/TP53.[1]
Publication Abstract from PubMed
The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form sub-complexes with PRC2 core components, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation. However, the mechanism of PRC2 recruitment to CpG islands is not fully understood. Here we solve 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 show that the extended homologous regions of both proteins fold into a winged-helix structure, which specifically binds to the unmethylated CpG motif but in a completely different manner from the canonical winged-helix DNA recognition motif. We also show that the PCL extended homologous domains are required for efficient recruitment of PRC2 to CpG island-containing promoters in mouse embryonic stem cells. Our research provides the first, to our knowledge, direct evidence to demonstrate that PCL proteins are crucial for PRC2 recruitment to CpG islands, and further clarifies the roles of these proteins in transcriptional regulation in vivo.
Polycomb-like proteins link the PRC2 complex to CpG islands.,Li H, Liefke R, Jiang J, Kurland JV, Tian W, Deng P, Zhang W, He Q, Patel DJ, Bulyk ML, Shi Y, Wang Z Nature. 2017 Sep 14;549(7671):287-291. doi: 10.1038/nature23881. Epub 2017 Sep 6. PMID:28869966[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cao R, Wang H, He J, Erdjument-Bromage H, Tempst P, Zhang Y. Role of hPHF1 in H3K27 methylation and Hox gene silencing. Mol Cell Biol. 2008 Mar;28(5):1862-72. Epub 2007 Dec 17. PMID:18086877 doi:http://dx.doi.org/10.1128/MCB.01589-07
- ↑ Li H, Liefke R, Jiang J, Kurland JV, Tian W, Deng P, Zhang W, He Q, Patel DJ, Bulyk ML, Shi Y, Wang Z. Polycomb-like proteins link the PRC2 complex to CpG islands. Nature. 2017 Sep 14;549(7671):287-291. doi: 10.1038/nature23881. Epub 2017 Sep 6. PMID:28869966 doi:http://dx.doi.org/10.1038/nature23881
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