WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development.

Journal article

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.

Authors: Wysocka, J; Swigut, T; Milne, T; Dou, Y; Zhang, X

• Publication status: Published
• Journal: Cell
• Volume: 121
• Issue: 6
• Pages: 859-872
• Publication date: 2005-06-01
• DOI: 10.1016/j.cell.2005.03.036
• EISSN: 1097-4172
• ISSN: 0092-8674
• Language: English
• Keywords: Histone-Lysine N-Methyltransferase; Animals; Xenopus laevis; Genes, Homeobox; Histones; Humans; Cell Line; Lysine; Nucleosomes; Methylation; Microfilament Proteins; Macromolecular Substances; Vertebrates; Heterotrimeric GTP-Binding Proteins