2016 Fiscal Year Final Research Report
Role of EED mutation in hematologic malignancy
| Project/Area Number |
26460391
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Kindai University (2016)
Hiroshima University (2014-2015) |
|---|
Principal Investigator |
UEDA Takeshi 近畿大学, 医学部, 講師 (60585149)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Keywords | エピジェネティクス |
|---|
| Outline of Final Research Achievements |
EED acts as a non-catalytic component of polycomb repressive complex 2 (PRC2) that is a central regulator of histone H3 Lys27 (H3K27) methylation associated with transcriptional repression. We previously identified EED Ile363Met (I363M) mutation in myelodysplastic syndrome and related diseases. In this study, to investigate the role of I363M in disease pathogenesis, we generated and analyzed EED I363M knock-in mice. As a result, the I363M mutation was shown to inhibit the propagation of trimethylated H3K27 repressive marks in vivo. In addition, we demonstrated that the heterozygotes enhanced hematopoietic stem/progenitor cell activity and contributed to increased susceptibility to leukemia, while the homozygotes resulted in embryonic lethality.
|
| Free Research Field |
医歯薬学
|
