Transformation of axial skeleton due to overexpression of bmi-1 in transgenic mice

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Abstract

THE oncogene bmi-l, which was originally found to be involved in B- and T-cell lymphoma formation1–3 encodes a protein with a domain of homology to the Drosophila protein Posterior sex combs (Psc) and its relative Suppressor 2 of Zeste (Su(z)2) (refs 4 and 5). Psc is a member of the Poly comb-group gene family, which is required to maintain the repression of homeotic genes that regulate the identities of Drosophila segments6. The possibility that bmi-l may play a similar role in vertebrates was suggested by our previous finding7 that mice lacking the bmi-l gene show posterior transformations of the axial skeleton. Here we report that transgenic mice overexpressing Bmi-l protein show the opposite phenotype, namely a dose-dependent anterior transformation of vertebral identity. The anterior expression boundary of the Hoxc-5 gene is shifted in the posterior direction, indicating that Bmi-l is involved in the repression Hox genes. We propose that Bmi-l is a member of a vertebrate Polycomb complex that regulates segmental identity by repressing Hox genes throughout development.

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