PUBLICATION
The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells
- Authors
- Yang, Z., Augustin, J., Chang, C., Hu, J., Shah, K., Chang, C.W., Townes, T., Jiang, H.
- ID
- ZDB-PUB-140821-4
- Date
- 2014
- Source
- Blood 124(13): 2025-33 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Differentiation*
- Cell Line, Tumor
- Cell Proliferation
- Cell Transformation, Neoplastic/genetics
- Cell Transformation, Neoplastic/metabolism
- Hematopoiesis
- Hematopoietic Stem Cells/cytology*
- Hematopoietic Stem Cells/metabolism*
- Histone-Lysine N-Methyltransferase/chemistry
- Histone-Lysine N-Methyltransferase/metabolism*
- Humans
- Leukemia/genetics
- Leukemia/metabolism
- Molecular Sequence Data
- Multiprotein Complexes/chemistry
- Multiprotein Complexes/metabolism*
- Myeloid-Lymphoid Leukemia Protein/chemistry
- Myeloid-Lymphoid Leukemia Protein/metabolism*
- Nuclear Proteins/chemistry
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism*
- Oncogene Proteins, Fusion/genetics
- Oncogene Proteins, Fusion/metabolism
- Protein Subunits/chemistry
- Protein Subunits/genetics
- Protein Subunits/metabolism*
- Sequence Alignment
- Zebrafish
- PubMed
- 25139354 Full text @ Blood
Citation
Yang, Z., Augustin, J., Chang, C., Hu, J., Shah, K., Chang, C.W., Townes, T., Jiang, H. (2014) The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells. Blood. 124(13):2025-33.
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/progenitor cells (HSC/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 co-injection of dpy30 mRNA. Taken together, our results establish a critical role of DPY30 in the proliferation and appropriate differentiation of hematopoietic progenitor cells as well as in animal hematopoiesis. Lastly, we also demonstrate a crucial role of DPY30 in the growth of several MLL1-fusion-mediated leukemia cell lines.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping