Two of the most abundant induced transcripts correspond to activated retro-elements. A B2-class SINE element, the murine equivalent of repetitive sequence DNA similar to human Alu, was induced during the first seven hours, reaching signal levels comparable to the globins. A VL30 endogenous retrotransposon was almost 20-fold induced over the course of the experiment. The probe sequence is similar to VL30 elements previously characterized as erythropoietin responsive in other cell lines 1,2. While not as abundant, a number of transcripts corresponding to intracisternal A particles, endogenous retroviruses, were also activated. The activation of endogenous retroviruses has been associated with loss of cytosine methylation by DNA methyltransferase-1 (Dnmt) 3 ,a gene which is repressed immediately after GATA-1 activation. The role of these apparently parasitic transcripts in normal erythropoiesis is not clear, but retrotransposition of these elements into cytokine genes and subsequent factor-independent transformation has been observed 4-7.
Viral-like sequences detected in G1E cells 0, 3, 7, 14, 21 and 30 hours after activation of GATA-1. 99849_at is VL30 like sequences, with homology to the MuLV LTR. 93909_at and 97181_at are similar to intracisternal A particles. The Affymetrix control sequence AFFX_MUR_B2 represents SINE B2 elements.
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|2. Park D, Lim R, Kim H. Rapid induction of mouse virus-like (VL30) element transcripts by erythropoietin in murine erythroid progenitor cells. Blood. 1993;82:77-83|
|3. Walsh C, Chaillet J, Bestor T. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nature Genetics. 1998;20:116-117|
|4. Pogue-Geile K, Gott J, Greenberger J. The role of intracisternal A-type particles in the evolution of factor-independent murine hematopoietic cell lines. Leukemia. 1998;12:4-12|
|5. Wang X, McCubrey J. Differential effects of retroviral long terminal repeats on interleukin 3 gene expression and autocrine transformation. 1997|
|6. Hirsch H, Nair A, Moroni C. Suppressible and nonsuppressible autocrine mast cell tumors are distinguished by insertion of an endogenous retroviral element (IAP) into the interleukin 3 gene. J Exp Med. 1993;178:403-411|
|7. Heberlein C, Kawai M, Franz M, Beck-Engeser G, Daniel C, Ostertag W, Stocking C. Retrotransposons as mutagens in the induction of growth autonomy in hematopoietic cells. Oncogene. 1990;5:1799-1807|
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