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Target Selection by Selective Binding

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Science's STKE  20 Jun 2000:
Vol. 2000, Issue 37, pp. tw8
DOI: 10.1126/stke.2000.37.tw8

Homeodomain proteins, such as Fushi tarazu (Ftz) are transcription factors that are major regulators of pattern formation early in development; however, homeodomain proteins alone have a low affinity and low specificity for DNA. Thus, their ability to regulate target gene activity is dependent on their interaction with cofactors. Two models for how these cofactors regulate homeodomain proteins are that the cofactors bind DNA specifically and direct the homeodomain proteins to these specific sites (selective binding model) or that the homeodomain proteins bind to many genes, and the cofactors act to control the transcriptional activity of the homeodomain proteins at specific sites (selective activation model). Nasiadka et al. replaced the activation domain of Ftz with the strong transcriptional activation domain of the herpes simplex virus protein VP16 and expressed this fusion protein in developing fly embryos to test the two models of regulation. The authors found that the FtzVP16 protein did not result in activation of genes not normally regulated by Ftz, suggesting that Ftz binding was controlling gene selection not selective activation. Two additional pieces of data in support of the selective binding model were that the phenotypes resulting from expression of FtzVP16 were predominantly the same as those caused by misexpression of Ftz and that homeodomain-deleted versions of Ftz and FtzVP16 were able to regulate Ftz target genes.

Nasiadka, A., Grill, A., and Krause, H.M. (2000) Mechanisms regulating target gene selection by the homeodomain-containing protein Fushi tarazu. Development 127: 2965-2976. [Online Journal]

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