2016 Fiscal Year Final Research Report
The functional difference among Pcgf family proteins in hematopoietic system
| Project/Area Number |
15K19544
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | ポリコーム / Pcgf1 / non-canonical PRC1 / エピジェネティクス |
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| Outline of Final Research Achievements |
We found that deletion of Pcgf1 in mice did not compromise self-renewal capacity of HSCs, but induced accumulation of granulocyte-macrophage progenitors and mature myeloid cells, eventually leading to the development of a lethal myeloproliferative neoplasm-like disease in mice. Detailed analysis of hematopoietic stem and progenitor cells (HSPCs) revealed skewing of HSC differentiation to myeloid lineages at the expense of B lymphocyte commitment in the absence of Pcgf1.Comprehensive analyses revealed that Cebpa, a master transcriptional factor for myeloid differentiation, was up-regulated following a reduction in H2AK119ub1 levels in Pcgf1-deficient HSPCs, resulting in the activation of C/EBPα targets in Pcgf1-deficient MPPs. These results indicate that Pcgf1 negatively regulates myeloid commitment of HSPCs to balance their multi-lineage differentiation
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| Free Research Field |
基礎医学
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