The Lysine Methylation Of WDR5 And Its Function Research

The lysine methylation of protein play an important role in gene transcriptional regulation,senescence and cancer,etc.This modification is mainly mediated by lysine methyltransferase.WDR5,as a components of methyltransferase complex,participates in histone H3K4 di-methylated and trimethylated and has a great effect on the process of embryonic stem cell self-renewal,bone development,breast cancer metastasis and the proliferation of bladder cancer cell lines,etc.But there was no posttranslational modification of WDR5 to regulate its biological function had been reported.Here,we reveal that the lysine 207 and 325 residues of WDR5 is mono-methylated by SETD6.Western blotting analyses shows that interference WDR5 expression results in H3K4me3 level decreasing.While overexpression of wild type WDR5 protein(WDR5 WT)lead to H3K4me3 level recover.However,the WDR5 protein bearing these monomethylation point mutations(WDR5 K207R,K325R)is obviouly not.Co-immunoprecipitation assays suggest the interaction between WDR5 and MLL1 has affected indistinctively.Furthermore,we discover that ectopic WDR5 WT overexpression promotes breast cancer cell MCF7 proliferation and migration,and the overexpression of WDR5 2KR has no significant change.Above all,our data presented in this thesis establish that lysine methylation at specific lysine residues of WDR5 by SETD6,and the lysine methylation of WDR5 enhance H3K4me3 in global level and breast cancer cell proliferation and migration.