J. Wysocka et al., "WDR5 associates with histone H3 methylated K4 and is essential for H3K4 methylation and vertebrate development," Cell, 121:859-72, 2005. (Cited in 96 papers)
David Allis from Rockefeller University and colleagues used a biochemical pull-down assay and found that the protein WDR5, a common part of histone methyltransferase complexes, associates specifically with dimethylated H3K4 nucleosomes. The absence of WDR5 in tadpoles resulted in developmental defects and abnormal Hox gene expression.
"The paper at the time was very provocative," says Danny Reinberg of the Robert Wood Johnson Medical School in New Jersey, because it was the first to tie vertebrate development to the recognition of a specific histone modification.
Three separate studies, including one by Allis and colleagues, later indicated that the specificity of WDR5 for dimethylated H3K4 is "plain wrong," Reinberg says. WDR5 bound "with almost no difference" in affinity to different methylated versions of H3K4, he adds.
WDR5's role in methylation is "still a mystery," Allis says. (See "The nucleosome untangled," The Scientist, May 2006.) "Maybe [WDR5 is] almost an intermediate stage reader that helps get that lysine presented" for methylation. Ali Shilatifard, of the Stowers Institute for Medical Research in Missouri, says WDR5 is likely an important scaffolding protein in methylation enzyme complexes.
|Some published findings since:|
|April and August 2006 - WDR5 binds to multiple methylated forms of H3K4 (Han et al., Molec Cell; Couture et al. and Ruthenburg et al., Nat Struct Mol Biol)|
|September 2006 - Dimethylated H3K4 forms extra hydrogen bonds with WDR5 (Couture et al., EMBO J)|
|January 2007 - Allis and colleagues propose that WDR5 is a histone modification intermediate (Ruthenburg et al., Molec Cell)|