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| | <StructureSection load='5uqd' size='340' side='right'caption='[[5uqd]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='5uqd' size='340' side='right'caption='[[5uqd]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5uqd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UQD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UQD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5uqd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UQD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UQD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</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]] 1.798Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dpy-21, CELE_Y59A8B.1, Y59A8B.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene></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=5uqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uqd OCA], [http://pdbe.org/5uqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uqd RCSB], [http://www.ebi.ac.uk/pdbsum/5uqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uqd ProSAT]</span></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=5uqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uqd OCA], [https://pdbe.org/5uqd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uqd RCSB], [https://www.ebi.ac.uk/pdbsum/5uqd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uqd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DPY21_CAEEL DPY21_CAEEL]] Required for X chromosome dosage compensation by reducing X-linked gene transcription in hermaphrodites throughout development (PubMed:14660541, PubMed:23028348, PubMed:3779843, PubMed:3478715, PubMed:26641248, PubMed:22393255). Might be involved in the regulation of histone H4 post-translational modifications on the X chromosome leading to transcriptional repression of X-linked genes (PubMed:22393255, PubMed:23028348, PubMed:26641248). Involved in the regulation of growth, fecundity and body fat metabolism downstream of the TOR complex 2 and the protein kinase sgk-1 pathway (PubMed:23884442). Also involved in male tail development (PubMed:6537930).<ref>PMID:14660541</ref> <ref>PMID:22393255</ref> <ref>PMID:23028348</ref> <ref>PMID:23884442</ref> <ref>PMID:26641248</ref> <ref>PMID:3478715</ref> <ref>PMID:3779843</ref> <ref>PMID:6537930</ref> | + | [https://www.uniprot.org/uniprot/DPY21_CAEEL DPY21_CAEEL] Required for X chromosome dosage compensation by reducing X-linked gene transcription in hermaphrodites throughout development (PubMed:14660541, PubMed:23028348, PubMed:3779843, PubMed:3478715, PubMed:26641248, PubMed:22393255). Might be involved in the regulation of histone H4 post-translational modifications on the X chromosome leading to transcriptional repression of X-linked genes (PubMed:22393255, PubMed:23028348, PubMed:26641248). Involved in the regulation of growth, fecundity and body fat metabolism downstream of the TOR complex 2 and the protein kinase sgk-1 pathway (PubMed:23884442). Also involved in male tail development (PubMed:6537930).<ref>PMID:14660541</ref> <ref>PMID:22393255</ref> <ref>PMID:23028348</ref> <ref>PMID:23884442</ref> <ref>PMID:26641248</ref> <ref>PMID:3478715</ref> <ref>PMID:3779843</ref> <ref>PMID:6537930</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Chromatin modification and higher-order chromosome structure play key roles in gene regulation, but their functional interplay in controlling gene expression is elusive. We have discovered the machinery and mechanism underlying the dynamic enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during C. elegans dosage compensation and demonstrated H4K20me1's pivotal role in regulating higher-order chromosome structure and X-chromosome-wide gene expression. The structure and the activity of the dosage compensation complex (DCC) subunit DPY-21 define a Jumonji demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals. Selective inactivation of demethylase activity eliminates H4K20me1 enrichment in somatic cells, elevates X-linked gene expression, reduces X chromosome compaction, and disrupts X chromosome conformation by diminishing the formation of topologically associating domains (TADs). Unexpectedly, DPY-21 also associates with autosomes of germ cells in a DCC-independent manner to enrich H4K20me1 and trigger chromosome compaction. Our findings demonstrate the direct link between chromatin modification and higher-order chromosome structure in long-range regulation of gene expression.
| + | |
| - | | + | |
| - | Dynamic Control of X Chromosome Conformation and Repression by a Histone H4K20 Demethylase.,Brejc K, Bian Q, Uzawa S, Wheeler BS, Anderson EC, King DS, Kranzusch PJ, Preston CG, Meyer BJ Cell. 2017 Aug 26. pii: S0092-8674(17)30877-2. doi: 10.1016/j.cell.2017.07.041. PMID:28867287<ref>PMID:28867287</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5uqd" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caeel]] | + | [[Category: Caenorhabditis elegans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Anderson, E C]] | + | [[Category: Anderson EC]] |
| - | [[Category: Bian, Q]] | + | [[Category: Bian Q]] |
| - | [[Category: Brejc, K]] | + | [[Category: Brejc K]] |
| - | [[Category: King, D S]] | + | [[Category: King DS]] |
| - | [[Category: Kranzusch, P]] | + | [[Category: Kranzusch PJ]] |
| - | [[Category: Meyer, B J]] | + | [[Category: Meyer BJ]] |
| - | [[Category: Preston, C G]] | + | [[Category: Preston CG]] |
| - | [[Category: Uzawa, S]] | + | [[Category: Uzawa S]] |
| - | [[Category: Wheeler, B S]] | + | [[Category: Wheeler BS]] |
| - | [[Category: H4k20me2 demethylase]]
| + | |
| - | [[Category: Jmjc]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
DPY21_CAEEL Required for X chromosome dosage compensation by reducing X-linked gene transcription in hermaphrodites throughout development (PubMed:14660541, PubMed:23028348, PubMed:3779843, PubMed:3478715, PubMed:26641248, PubMed:22393255). Might be involved in the regulation of histone H4 post-translational modifications on the X chromosome leading to transcriptional repression of X-linked genes (PubMed:22393255, PubMed:23028348, PubMed:26641248). Involved in the regulation of growth, fecundity and body fat metabolism downstream of the TOR complex 2 and the protein kinase sgk-1 pathway (PubMed:23884442). Also involved in male tail development (PubMed:6537930).[1] [2] [3] [4] [5] [6] [7] [8]
References
- ↑ Yonker SA, Meyer BJ. Recruitment of C. elegans dosage compensation proteins for gene-specific versus chromosome-wide repression. Development. 2003 Dec;130(26):6519-32. PMID:14660541 doi:http://dx.doi.org/10.1242/dev.00886
- ↑ Wells MB, Snyder MJ, Custer LM, Csankovszki G. Caenorhabditis elegans dosage compensation regulates histone H4 chromatin state on X chromosomes. Mol Cell Biol. 2012 May;32(9):1710-9. doi: 10.1128/MCB.06546-11. Epub 2012 Mar 5. PMID:22393255 doi:http://dx.doi.org/10.1128/MCB.06546-11
- ↑ Vielle A, Lang J, Dong Y, Ercan S, Kotwaliwale C, Rechtsteiner A, Appert A, Chen QB, Dose A, Egelhofer T, Kimura H, Stempor P, Dernburg A, Lieb JD, Strome S, Ahringer J. H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation. PLoS Genet. 2012 Sep;8(9):e1002933. doi: 10.1371/journal.pgen.1002933. Epub 2012 , Sep 13. PMID:23028348 doi:http://dx.doi.org/10.1371/journal.pgen.1002933
- ↑ Webster CM, Wu L, Douglas D, Soukas AA. A non-canonical role for the C. elegans dosage compensation complex in growth and metabolic regulation downstream of TOR complex 2. Development. 2013 Sep;140(17):3601-12. doi: 10.1242/dev.094292. Epub 2013 Jul 24. PMID:23884442 doi:http://dx.doi.org/10.1242/dev.094292
- ↑ Kramer M, Kranz AL, Su A, Winterkorn LH, Albritton SE, Ercan S. Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans. PLoS Genet. 2015 Dec 7;11(12):e1005698. doi: 10.1371/journal.pgen.1005698., eCollection 2015 Dec. PMID:26641248 doi:http://dx.doi.org/10.1371/journal.pgen.1005698
- ↑ Donahue LM, Quarantillo BA, Wood WB. Molecular analysis of X chromosome dosage compensation in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7600-4. PMID:3478715
- ↑ Meyer BJ, Casson LP. Caenorhabditis elegans compensates for the difference in X chromosome dosage between the sexes by regulating transcript levels. Cell. 1986 Dec 26;47(6):871-81. PMID:3779843
- ↑ Meneely PM, Wood WB. An autosomal gene that affects X chromosome expression and sex determination in Caenorhabditis elegans. Genetics. 1984 Jan;106(1):29-44. PMID:6537930
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