title: The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells.
abstract: Epigenetic mechanisms, including histone modifications, have emerged as important factors influencing cell fate determination. The functional role of H3K4 methylation, however, remains largely unclear in the maintenance and differentiation of hematopoietic stem cells (HSCs)/hematopoietic progenitor cells (HPCs). Here we show that DPY30, a shared core subunit of the SET1/MLL family methyltransferase complexes and a facilitator of their H3K4 methylation activity, is important for ex vivo proliferation and differentiation of human CD34(+) HPCs. DPY30 promotes HPC proliferation by directly regulating the expression of genes critical for cell proliferation. Interestingly, while DPY30 knockdown in HPCs impaired their differentiation into the myelomonocytic lineage, it potently promoted hemoglobin production and affected the kinetics of their differentiation into the erythroid lineage. In an in vivo model, we show that morpholino-mediated dpy30 knockdown resulted in severe defects in the development of the zebrafish hematopoietic system, which could be partially rescued by coinjection of dpy30 messenger RNA. Taken together, our results establish a critical role of DPY30 in the proliferation and appropriate differentiation of hematopoietic progenitor cells and in animal hematopoiesis. Finally, we also demonstrate a crucial role of DPY30 in the growth of several MLL1-fusion-mediated leukemia cell lines.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham Stem Cell Institute, and.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham Stem Cell Institute, and.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Augustin
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, Birmingham, AL.
authors.forename: Chenbei
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham Stem Cell Institute, and.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham Stem Cell Institute, and.
authors.forename: Kushani
authors.initials: K
authors.lastname: Shah
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham Stem Cell Institute, and.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham Stem Cell Institute, and.
authors.forename: Tim
authors.initials: T
authors.lastname: Townes
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham Stem Cell Institute, and.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors; D015027:Zebrafish
chemical_list: C507432:DPY30 protein, human; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D021122:Protein Subunits; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase