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Histone H3 lysine 4 (K4) methylation has been linked to the transcriptional activation in a variety of eukaryotic species. Here we show that a common component of MLL1, MLL2, and hSet1 H3 K4 methyltransferase complexes, the WD40-repeat protein WDR5, directly associates with histone H3 di- and trimethylated at K4 and with H3-K4-dimethylated nucleosomes. WDR5 is required for binding of the methyltransferase complex to the K4-dimethylated H3 tail as well as for global H3 K4 trimethylation and HOX gene activation in human cells. WDR5 is essential for vertebrate development, in that WDR5-depleted X. laevis tadpoles exhibit a variety of developmental defects and abnormal spatial Hox gene expression. Our results are the first demonstration that a WD40-repeat protein acts as a module for recognition of a specific histone modification and suggest a mechanism for reading and writing an epigenetic mark for gene activation.

Original publication

DOI

10.1016/j.cell.2005.03.036

Type

Journal article

Journal

Cell

Publication Date

17/06/2005

Volume

121

Pages

859 - 872

Keywords

Animals, Cell Line, Genes, Homeobox, Heterotrimeric GTP-Binding Proteins, Histone-Lysine N-Methyltransferase, Histones, Humans, Lysine, Macromolecular Substances, Methylation, Microfilament Proteins, Nucleosomes, Vertebrates, Xenopus laevis