Virus-like Transcripts

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.

References

1. Staplin W, Hodgson C, Knezetic J. Conserved, erythropoietin-responsive VL30 promoters isolated from erythroid progenitor cells. Blood Cells, Molecules and Diseases. 2002;28:275-282
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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Please direct all comments to: John Welch, M.D., Ph.D.
Last modification: May 21, 2004