Chimeric transcription factor

Chromosomal breakpoints occur within the coding regions of the transcription factors, producing a fusion gene that encodes a chimeric transcription factor with altered function. 

E. S. Massuda, E. J. Dunphy, R. A. Redman, J. J. Schreiber, L. E. Nauta, F. G. Barr, I. H. Maxwell, and T. P. Cripe, Regulated expression of the diphtheria toxin A chain by a tumor-specific chimeric transcription factor results in selective toxicity for alveolar rhabdomyosarcoma cells, Proc. Natl. Acad. Sci. USA 94 14701 (1997). 

V. Jerome, and R. Muller, Tissue-specific, cell cycle-regulated chimeric transcription factors for the targeting of gene expression to tumor cells, Hum. Gene Ther. 9 2653 (1998). 

Other examples are fusions of the e2a gene, which encodes the E2A transcription factor, a cell-cycle-regulating factor. The e2a gene fuses with genes that encode other transcription factors, such as HLF (hepatocyte leukaemia factor). This causes overexpression of the chimeric transcription factor. Juxtaposition of the trawi-activation domains of E2A and HLE in the E2A-HLF fusion protein results in mismatched heterodimerization and in competition between dimerization partners of E2A-HLF. These gene fusions are the most common changes in the chromosomes of children with acute lymphoblastic leukaemia (ALL). 

Nourse, J., Mellentin, J.D., Galili, N., Wilkinson, J., Starbridge, E., Smith, S.D., Cleary, M.L. 1990. Chromosomal translocation t(l 19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 60, 535-545. 

What do the results from the experiments with the Gal4-VP16 chimeric transcription factor reveal about the mechanisms of transcriptional regulation ... 

For these reasons, we attempted to increase the levels of isoflavones in soybean. By combining expression of a chimeric transcription factor (CRC), which acts to increase flux through the phenylpropanoid pathway with the suppression of a competing pathway via RNAi mediated silencing of flavanone 3-hydroxylase, levels of isoflavones were shown to accumulate in the seed to levels that were 3-4 times higher than in wild type soybeans. 

Aside from the immunohistochemical detection of muscle-specific transcription factors as described earlier, no other genomic-immunohistochemical diagnostic applications are currently available. The PAX-FKHR chimeric transcripts are, to date, not detectable by immunohistochemistry. 

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