Nature Structural & Molecular Biology
- 13, 704 - 712 (2006)
Published online: 9 July 2006; | doi:10.1038/nsmb1119
Histone H3 recognition and presentation by the WDR5 module of the MLL1 complexAlexander J Ruthenburg1, 2, Wooikoon Wang3, Daina M Graybosch1, Haitao Li3, C David Allis2, Dinshaw J Patel3 & Gregory L Verdine1, 41
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA. 2
Laboratory of Chromatin Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA. 3
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. 4
Department of Molecular and Cellular Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Correspondence should be addressed to Gregory L Verdine verdine@chemistry.harvard.edu
WDR5 is a core component of SET1-family complexes that achieve transcriptional activation via methylation of histone H3 on N of Lys4 (H3K4). The role of WDR5 in the MLL1 complex has recently been described as specific recognition of dimethyl-K4 in the context of a histone H3 amino terminus; WDR5 is essential for vertebrate development, Hox gene activation and global H3K4 trimethylation. We report the high-resolution X-ray structures of WDR5 in the unliganded form and complexed with histone H3 peptides having unmodified and mono-, di- and trimethylated K4, which together provide the first comprehensive analysis of methylated histone recognition by the ubiquitous WD40-repeat fold. Contrary to predictions, the structures reveal that WDR5 does not read out the methylation state of K4 directly, but instead serves to present the K4 side chain for further methylation by SET1-family complexes.
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