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The E2A-HLF oncogenic fusion gene, generated by t(17;19)(q22;p13) translocation in childhood B-cell acute lymphoblastic leukemia with a very poor prognosis, encodes a chimeric transcription factor in which the transactivation domains of immunoglobulin enhancer-binding factor (E2A) are fused to the DNA-binding and dimerization domain of hepatic leukemia factor (HLF). E2A-HLF was shown to have an anti-apoptotic effect. However, the molecular mechanism underlying E2A-HLF-mediated leukemogenesis remains unclear. We identified the transcriptional coactivator Eya2, the forced expression of which is known to immortalize mouse hematopoietic stem/progenitor cells (HSPCs), as a direct target molecule downstream of E2A-HLF. E2A-HLF-immortalized mouse HSPCs expressed Eya2 at a high level in the aberrant self-renewal program. Chromatin immunoprecipitation-quantitative polymerase chain reaction and a reporter assay revealed that E2A-HLF enhanced the Eya2 expression by binding to the promoter region containing the E2A-HLF-binding consensus sequence. Eya2 knockdown in E2A-HLF-immortalized cells resulted in reduced colony-forming efficiency. These results suggest a critical role of Eya2 in E2A-HLF-mediated leukemogenesis.
本文/Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine,
27p
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2019-11-04T14:30:53+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション