2005 Fiscal Year Final Research Report Summary
analysis of leukemogenesis by the expression of EVI1/MEL1S, the PR domain-defective proteins, in EVI1/MEL1 gene family
| Project/Area Number |
16590950
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
NISHIKATA Ichiro University of Miyazaki, Medicine, Research associate, 医学部, 助手 (50253844)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAGA Toshiyuki University of Miyazaki, Med., Research associate, 医学部, 助手 (70363596)
MORISHITA Kazuhiro University of Miyazaki, Med., Professor, 医学部, 教授 (80260321)
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| Project Period (FY) |
2004 – 2005
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| Keywords | EVI1 / MEL1S / Mice lacking EVI1 / Hematopoietic stem cells / GATA-2 / HDAC / TSA / leukemogenesis |
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| Research Abstract |
The ecotropic viral integration site-1 (EVI1) and MDS1/EVI1-like gene 1 (MEL1) were identified as transcriptional regulators that were the causative factors in pathogenesis of myeloid leukemia. However, the molecular basis of their transcriptional functions has remained elusive. Recently, we have shown that EVI1 directly regulates the expression of GATA-2 both in vitro and in vivo and plays an important role in proliferation and differentiation of the hematopoietic stem cell by the analysis of mice lacking EVI1. Here, we show that EVI1 binds to its DNA consensus sequence located around 6-7 kb upstream region of the GATA-2 IS exon and up-regulates the expression of GATA-2 gene in EML-C1, a murine multipotent progenitor cell line, HEL, a human erythroleukemia cell line. Similarly, EVI1 was related to the expression of GATA-2 gene in mouse NSF58 and M1S2, human AML1 and Kasumi-3, MOLM1, EVI1-overexpressing leukemia cell lines. But Overexpression of MEL1S, PR domain-defective short form, as same as EVI1, in L-G3, a IL-3-dependent murine myeloid cell line, blocks G-CSF-induced myeloid differentiation and down-regulate the expression of GATA-2 gene. These findings highlight the relationship between the expression of GATA-2 gene regulated by EVI1/MEL1S and the interaction of EVI1/MEL1S and histone acetyltransferases/HDAC and how these factors affect the gene expression and leukemogenesis of EVI1/MEL1S in leukemia cells.
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Research Products
(2 results)
