| Structural highlights
Function
[DPY30_HUMAN] As part of the MLL1/MLL complex, involved in the methylation of histone H3 at 'Lys-4', particularly trimethylation. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. May play some role in histone H3 acetylation. In a teratocarcinoma cell, plays a crucial role in retinoic acid-induced differentiation along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci. May also play an indirect or direct role in endosomal transport.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The conserved DPY-30 is an essential component of the dosage compensation complex that balances the X-linked gene expression by regulation of the complex formation in Caenorhabditis elegans. The human DPY-30-like protein (DPY-30L) homolog is a conserved member of certain histone methyltransferase (HMT) complexes. In the human MLL1 (mixed-lineage leukemia-1) HMT complex, DPY-30L binds to the BRE2 homolog ASH2L in order to regulate histone 3-lysine 4 trimethylation. We have determined the 1.2-A crystal structure of the human DPY-30L C-terminal domain (DPY-30L(C)). The DPY-30L(C) structure, harboring the conserved DPY-30 motif, is composed of two alpha-helices linked by a sharp loop and forms a typical X-type four-helix bundle required for dimer formation. DPY-30L(C) dimer formation is largely mediated by an extensive hydrophobic interface with some additional polar interactions. The oligomerization of DPY-30L(C) in solution, together with its reported binding to ASH2L, leads us to propose that the hydrophobic surface of the dimer may provide a platform for interaction with ASH2L in the MLL1 HMT complex.
Crystal structure of the C-terminal domain of human DPY-30-like protein: A component of the histone methyltransferase complex.,Wang X, Lou Z, Dong X, Yang W, Peng Y, Yin B, Gong Y, Yuan J, Zhou W, Bartlam M, Peng X, Rao Z J Mol Biol. 2009 Jul 17;390(3):530-7. Epub 2009 May 27. PMID:19481096[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Patel A, Dharmarajan V, Vought VE, Cosgrove MS. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. J Biol Chem. 2009 Sep 4;284(36):24242-56. Epub 2009 Jun 25. PMID:19556245 doi:M109.014498
- ↑ Xu Z, Gong Q, Xia B, Groves B, Zimmermann M, Mugler C, Mu D, Matsumoto B, Seaman M, Ma D. A role of histone H3 lysine 4 methyltransferase components in endosomal trafficking. J Cell Biol. 2009 Aug 10;186(3):343-53. doi: 10.1083/jcb.200902146. Epub 2009 Aug, 3. PMID:19651892 doi:http://dx.doi.org/10.1083/jcb.200902146
- ↑ Jiang H, Shukla A, Wang X, Chen WY, Bernstein BE, Roeder RG. Role for Dpy-30 in ES cell-fate specification by regulation of H3K4 methylation within bivalent domains. Cell. 2011 Feb 18;144(4):513-25. doi: 10.1016/j.cell.2011.01.020. PMID:21335234 doi:http://dx.doi.org/10.1016/j.cell.2011.01.020
- ↑ Wang X, Lou Z, Dong X, Yang W, Peng Y, Yin B, Gong Y, Yuan J, Zhou W, Bartlam M, Peng X, Rao Z. Crystal structure of the C-terminal domain of human DPY-30-like protein: A component of the histone methyltransferase complex. J Mol Biol. 2009 Jul 17;390(3):530-7. Epub 2009 May 27. PMID:19481096 doi:10.1016/j.jmb.2009.05.061
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