WDR5 high expression and its effect on tumorigenesis in leukemia
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Zheng Ge1,2,3, Evelyn J. Song2, Yuka Imamura Kawasawa4, Jianyong Li3, Sinisa Dovat2, Chunhua Song2
1Department of Hematology (Key Department of Jiangsu Medicine), Zhongda Hospital, Southeast University Medical School, Nanjing, Jiangsu, China
2Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, USA
3Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial Hospital, Nanjing, China
4Pennsylvania State Hershey Genome Sciences Facility, Pennsylvania State College of Medicine, Hershey, PA, USA
Chunhua Song, email: [email protected]
Sinisa Dovat, email: [email protected]
Jianyong Li, email: [email protected]
Keywords: WDR5, H3K4me3, MLL, leukemia
Received: March 16, 2016 Accepted: April 27, 2016 Published: May 12, 2016
WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription. However, the oncogenic effect of WDR5 in leukemia remains largely unknown. Here, we found WDR5 expression is increased in leukemia patients. High expression of WDR5 is associated with high risk leukemia; Patients with WDR5 and MLL1 high expression have poor complete remission rate. We further identified the global genomic binding of WDR5 in leukemic cells and found the genomic co-localization of WDR5 binding with H3K4me3 enrichment. Moreover, WDR5 knockdown by shRNA suppresses cell proliferation, induces apoptosis, inhibits the expression of WDR5 targets, and blocks the H3K4me3 enrichment on the promoter of its targets. We also observed the positive correlation of WDR5 expression with these targets in the cohort study of leukemia patients. Our data reveal that WDR5 may have oncogenic effect and WDR5-mediated H3K4 methylation plays an important role in leukemogenesis.
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