title: WDR5 high expression and its effect on tumorigenesis in leukemia.
abstract: 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.
authors.affiliation: Department of Hematology (Key Department of Jiangsu Medicine), Zhongda Hospital, Southeast University Medical School, Nanjing, Jiangsu, China.|Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, USA.|Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial Hospital, Nanjing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Evelyn J
authors.initials: EJ
authors.lastname: Song
authors.affiliation: Pennsylvania State Hershey Genome Sciences Facility, Pennsylvania State College of Medicine, Hershey, PA, USA.
authors.forename: Yuka Imamura
authors.initials: YI
authors.lastname: Kawasawa
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Provincial Hospital, Nanjing, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Sinisa
authors.initials: S
authors.lastname: Dovat
authors.affiliation: Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Song
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D063646:Carcinogenesis; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000503:physiopathology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D012074:Remission Induction; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C502547:WDR5 protein, human; D011495:Histone-Lysine N-Methyltransferase
keywords: H3K4me3; MLL; WDR5; leukemia