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| | ==Crystal structure of the Bromo-PWWP of the mouse zinc finger MYND-type containing 11 isoform alpha in complex with histone H3.3K36me3== | | ==Crystal structure of the Bromo-PWWP of the mouse zinc finger MYND-type containing 11 isoform alpha in complex with histone H3.3K36me3== |
| - | <StructureSection load='4n4i' size='340' side='right' caption='[[4n4i]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4n4i' size='340' side='right'caption='[[4n4i]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4n4i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N4I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N4I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4n4i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N4I FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4n4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n4i OCA], [https://pdbe.org/4n4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n4i RCSB], [https://www.ebi.ac.uk/pdbsum/4n4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n4i ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n4g|4n4g]], [[4n4h|4n4h]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BS69, Zmynd11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4n4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n4i OCA], [http://pdbe.org/4n4i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n4i RCSB], [http://www.ebi.ac.uk/pdbsum/4n4i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n4i ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ZMY11_MOUSE ZMY11_MOUSE]] Corepressor of transcription (Probable). May be involved in chromatin remodeling through association with several remodeling factors (By similarity). | + | [https://www.uniprot.org/uniprot/ZMY11_MOUSE ZMY11_MOUSE] Corepressor of transcription (Probable). May be involved in chromatin remodeling through association with several remodeling factors (By similarity). |
| | <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: Lk3 transgenic mice]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Li, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, Y]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ren, Y]] | + | [[Category: Li H]] |
| - | [[Category: Histone h3 3-specific]] | + | [[Category: Li Y]] |
| - | [[Category: Tandem bromodomain-zinc finger-pwwp motif]] | + | [[Category: Ren Y]] |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
ZMY11_MOUSE Corepressor of transcription (Probable). May be involved in chromatin remodeling through association with several remodeling factors (By similarity).
Publication Abstract from PubMed
Recognition of modified histones by 'reader' proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.
ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression.,Wen H, Li Y, Xi Y, Jiang S, Stratton S, Peng D, Tanaka K, Ren Y, Xia Z, Wu J, Li B, Barton MC, Li W, Li H, Shi X Nature. 2014 Apr 10;508(7495):263-8. doi: 10.1038/nature13045. Epub 2014 Mar 2. PMID:24590075[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wen H, Li Y, Xi Y, Jiang S, Stratton S, Peng D, Tanaka K, Ren Y, Xia Z, Wu J, Li B, Barton MC, Li W, Li H, Shi X. ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression. Nature. 2014 Apr 10;508(7495):263-8. doi: 10.1038/nature13045. Epub 2014 Mar 2. PMID:24590075 doi:http://dx.doi.org/10.1038/nature13045
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