MPC2, A NEW MURINE HOMOLOG OF THE DROSOPHILA POLYCOMB PROTEIN IS A MEMBER OF THE MOUSE POLYCOMB TRANSCRIPTIONAL REPRESSOR COMPLEX

The evolutionarily conserved polycomb and trithorax-group genes are re quired to maintain stable expression patterns of homeotic genes and ot her target genes throughout development. Here, we report the cloning a nd characterization of a novel mouse polycomb homolog, MPc2, in additi on to the previously described M33 polycomb gene. Co-immunoprecipitati ons and subnuclear co-localization studies show that MPc2 interacts wi th the mouse polycomb-group oncoprotein Bmi1 and is a new member of th e mouse polycomb multiprotein complex. Gal4DB- MPc2 or -M33 fusion pro teins mediate a five-to tenfold repression of stably integrated-report er constructs carrying GAL4 binding sites, demonstrating that these pr oteins are transcriptional repressors. The MPc2 gene is localized on c hromosome 11, in close proximity to the classical mouse mutations tail short (Ts) and rabo torcido (Rbt). Ts and Xbt hemizygous mice display anemia and transformations of the axial skeleton reminiscent of pheno types observed in mice with mutated polycomb or trithorax-group :genes , suggesting that MPc2 is a candidate gene for Ts and Rbt. (C) 1997 Ac ademic Press Limited.