Biological Role
EVI1 is a proto-oncogene conserved across humans, mice, and rats, sharing 91% homology in nucleotide sequence and 94% homology in amino acid sequence between humans and mice. It is a transcription factor localized to the nucleus and binds DNA through specific conserved sequences of GACAAGATA with the potential to interact with both corepressors and coactivators.
Embryogenesis: The role of EVI1 in embryogenesis and development is not completely understood, but it has been shown that EVI1 deficiency in mice is an embryonic lethal mutation, characterized primarily by widespread hypocellularity and poor/disrupted development of the cardiovascular and neural system. EVI1 is highly expressed in the murine embryo, found in the urinary system, lungs, and heart, but is only minutely detectable in most adult tissues, indicating a likely role in tissue development. EVI1 and the fusion transcript MDS1-EVI1 are both expressed in the adult human kidney, lung, pancreas, brain, and ovaries.
Cell cycle and differentiation: In vitro experiments using both human and mouse cell lines have shown that EVI1 prevents the terminal differentiation of bone marrow progenitor cells to granulocytes and erythroid cells, however it favors the differentiation of hematopoietic cell to megakaryocytes. The chimeric gene of AML1-MDS1-EVI1 (AME) formed by the chromosomal translocation (3;21)(q26;q22) has also been shown in vitro to upregulate the cell cycle and block granulocytic differentiation of murine hematopoietic cells, as well as to delay the myeloid differentiation of bone marrow progenitors.
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