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Publication : A role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton.

First Author  Akasaka T Year  1996
Journal  Development Volume  122
Issue  5 Pages  1513-22
PubMed ID  8625838 Mgi Jnum  J:33159
Mgi Id  MGI:80640 Doi  10.1242/dev.122.5.1513
Citation  Akasaka T, et al. (1996) A role for mel-18, a Polycomb group-related vertebrate gene, during the anteroposterior specification of the axial skeleton. Development 122(5):1513-1522
abstractText  Segment identity in both invertebrates and vertebrates is conferred by spatially restricted distribution of homeotic gene products. In Drosophila, the expression of Homeobox genes during embryogenesis is initially induced by segmentation gene products and then maintained by Polycomb group and Trithorax group gene products, Polycomb group gene homologs are conserved in vertebrates, Murine mel-18 and closely related bmi-l are homologous to posterior sex combs and suppressor two of zeste, Mel-18 protein mediates a transcriptional repression via direct binding to specific DNA sequences, To gain further insight into the function of Mel-18, we have inactivated the mel-Ig locus by homologous recombination, Mice lacking mel-18 survive to birth and die around 4 weeks after birth after exhibiting strong growth retardation. Similar to the Drosophila posterior sex combs mutant, posterior transformations of the axial skeleton were reproducibly observed in mel-18 mutants. The homeotic transformations were correlated with ectopic expression of Homeobox cluster genes along the anteroposterior axis in the developing paraxial mesoderm, Surprisingly, mel-18- deficient phenotypes are reminiscent of bmi-1 mutants, These results indicate that the vertebrate Polycomb group genes mel-18 and bmi-1, like Drosophila Polycomb group gene products, might play a crucial role in maintaining the silent state of Homeobox gene expression during paraxial mesoderm development.
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