A Role for WDR5 in Integrating Threonine 11 Phosphorylation to Lysine 4 Methylationon Histone H3 and in Prostate Cancer

ABSTRACT: Upon androgen stimulation, PKN1-mediated histone H3 threonine 11 phosphorylation (H3T11P) promotes AR target genes activation. However, the underlying mechanism is not completely understood. Here, we show that WDR5, a subunit of the SET1/MLL complex, interacts with H3T11P and this interaction facilitates the recruitment of the SET1/MLL complex and subsequent H3K4 trimethylation (H3K4me3). Using ChIP-seq, we find that androgen stimulation results in a six-fold increase in the number of H3T11P-marked regions and induces WDR5 colocalization to one third of H3T11P-enriched promoters, thus establishing a genome-wide relationship between H3T11P and recruitment of WDR5. Accordingly, PKN1 knock-down or chemical inhibition severely blocks WDR5 association and H3K4me3 on AR target genes. Finally, WD

ORGANISM(S): Homo sapiens

SUBMITTER: Grant Baish 

PROVIDER: E-GEOD-55279 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress