Transformation of axial skeleton due to overexpression of bmi-1 in transgenic mice.
The oncogene bmi-1, which was originally found to be involved in B- and T-cell lymphoma formation 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 Polycomb-group gene family, which is required to maintain the repression of homeotic genes that regulate the identities of Drosophila segments. The possibility that bmi-1 may play a similar role in vertebrates was suggested by our previous finding that mice lacking the bmi-1 gene show posterior transformations of the axial skeleton. Here we report that transgenic mice overexpressing Bmi-1 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-1 is involved in the repression of Hox genes. We propose that Bmi-1 is a member of a vertebrate Polycomb complex that regulates segmental identity by repressing Hox genes throughout development.
Alkema
M J
MJ
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
van der Lugt
N M
NM
Bobeldijk
R C
RC
Berns
A
A
van Lohuizen
M
M
D000818:Animals; D001368:Axis, Cervical Vertebra / Q000002:abnormalities; D001270:Cervical Atlas / Q000002:abnormalities; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005801:Genes, Homeobox; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012097:Repressor Proteins; D013131:Spine / Q000002:abnormalities* / Q000196:embryology; D013904:Thoracic Vertebrae / Q000002:abnormalities
C489421:Bmi1 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1