Disease relevance of Evi1

• Integrations into Evi1 were restricted to myeloid leukemias, whereas those in Evi11/Cb2 and Evi12 were identified in myeloid as well as T-lymphoid leukemias [1].
• The chromosomal location of Evi-1, a common site of ecotropic viral integration in AKXD murine myelogenous leukemias, was determined by recombinant inbred and conventional backcross analyses [2].
• Five of 37 cell lines contained proviruses in a common viral integration site termed the ecotropic virus integration 1 site (Evi-1) [3].
• To elucidate whether expression of Evi1 is involved in early neuroectodermal or mesodermal differentiation, we used murine embryonal carcinoma P19 cells as a model for the study of early embryonic differentiation [4].
• Unique expression of the human Evi-1 gene in an endometrial carcinoma cell line: sequence of cDNAs and structure of alternatively spliced transcripts [5].

High impact information on Evi1

• We therefore investigate the role and authentic target genes of Evi1 in hematopoiesis using Evi1-/- mice, which die at embryonic day 10 [6].
• We herein show that Evi1 is predominantly expressed in hematopoietic stem cells (HSCs) in embryos and adult bone marrows, suggesting a physiological role of Evi1 in HSCs [6].
• Restoration of the Evi1 or GATA-2 expression in Evi1-/- HSCs could prevent the failure of in vitro maintenance and proliferation of HSC through upregulation of GATA-2 expression [6].
• The ecotropic viral integration site-1 (Evi1) is an oncogenic transcription factor in murine and human myeloid leukemia [6].
• Retroviral integration in murine myeloid tumors to identify Evi-1, a novel locus encoding a zinc-finger protein [7].

Biological context of Evi1

• Taken together, our results present the first evidence of Evi1 disturbing normal erythropoiesis in vivo and provides evidence for cooperative potential of Evi1 in tumor progression [8].
• The full-length Evi1 transcript encodes a putative transcription factor, containing ten zinc finger motifs found within two domains of the protein [9].
• The Evi1 proto-oncogene is required at midgestation for neural, heart, and paraxial mesenchyme development [9].
• These data suggest that Evi1 has important roles in general cell proliferation, vascularization, and cell-specific developmental signaling, at midgestation [9].
• To determine the biological function of the Evi1 proto-oncogene, the full-length, but not an alternately spliced, transcript was disrupted using targeted mutagenesis in embryonic stem cells [9].

Anatomical context of Evi1

• It is suggested that Evi-1 plays important roles in embryogenesis and transformation of myeloid cells [10].
• In contrast, few Evi-1 rearrangements were detected in the DNA of T- or B-cell tumors [11].
• Thus, the overexpression of Evi1 leads to neural differentiation of P19 cells and blocks further differentiation into astrocytes by RA treatment, suggesting that Evi1 might be an important transcription factor for regulation of early neuroectodermal differentiation [4].
• In order to evaluate transforming activity of this protein, AML1/Evi-1 was introduced into Rat1 fibroblasts [12].
• In this paper three examples are presented of human acute myelogenous leukemias presenting common characteristics: (i) high Evi-1 mRNA expression; (ii) chromosomal abnormalities t(3;3)(q21;q26) or inv(3;3)(q21-22;q26); and (iii) high platelet counts and dystrophic megakaryocytes [13].

Associations of Evi1 with chemical compounds

• After retinoic acid (RA) treatment with aggregation, expression of Evi1 was detected during neural differentiation in P19 cells [4].
• However, Evi1 was not expressed in P19 cells during mesodermal differentiation after DMSO treatment with aggregation [4].
• In the studies presented here we also show that Evi-1 can repress GATA-1-dependent transactivation in transient chloramphenicol acetyltransferase assays [14].
• Both GAL4DBD/Evi-1 fusion and non-fusion proteins have been used to map the repressor activity to a proline-rich region located within amino acids 514-724 between the ZF1 and ZF2 domains [15].

Regulatory relationships of Evi1

• Erythroid defects and increased retrovirally-induced tumor formation in Evi1 transgenic mice [8].
• Retroviral insertions in the CB-1/Fim-3 common site of integration activate expression of the Evi-1 gene [16].
• After incubation with RA with aggregation, the Evi1 clones expressed microtubule-associated protein-2 continuously but did not express glial fibrillary acidic protein as an astrocyte marker protein until 12 days of culture [4].

Other interactions of Evi1

• These results indicate that Evi-1 raises AP-1 activity [10].
• To determine the effect of enforced expression of Evi1 in vivo, we developed a transgenic mouse model utilizing the murine Sca-1 (Ly-6E.1) promoter [8].
• We mapped Evi-1 to a location approximately 15 cM distal to the carbonic anhydrase locus on murine Chromosome 3 [2].
• Interestingly, Fim-3 is tightly linked to Evi-1, another common integration site of ecotropic virus involved in another model of mouse myeloid leukemogenesis [17].
• We report here the functional analyses of AML1/Evi-1 [18].

Analytical, diagnostic and therapeutic context of Evi1

• These results correlated with whole-mount in situ hybridization analyses of embryos which showed expression of the Evi1 proto-oncogene in embryonic mesoderm and neural crest-derived cells associated with the peripheral nervous system [9].
• The possible basis for the unique expression of the Evi-1 gene by HEC-1 cells could not be determined by karyotype or Southern blot analysis [5].
• By sequence analysis, we found that one Evi-1 cDNA (E29) had an internal deletion of 972 nucleotides when compared to the full-length sequence previously published by Morishita et al [19].
• To evaluate the sequence specificity of Evi-1 binding and potentially identify genomic targets, whole-genome PCR was utilized to isolate multiple Sau3A fragments which specifically bind to the amino-terminal zinc finger domain [20].

References