In Drosophila, Polycomb (Pc-g) gene family encodes chromatin proteins that are required for the repression of homeotic loci in embryonic development. Mel-18 and Bmi-1, mammalian homologs of Drosophila Pc-g group proteins, are similarly expressed during development and implicated in the regulation of gene expression, axial skeleton development, control of proliferation and survival of haematopoietic cells. Mel-18 directly binds to DNA through a RING-finger motif and preferentially associates with juxtaposed enhancer elements on various genes, including Bcl-2, c-Myc and Hox. Mel-18 is an immediate early response gene within the c-Myc/Cdc25 signaling cascade that exhibits tumor suppressor activity and negatively regulates cell cycle progression by blocking S phase entry. Alternatively, Bmi-1 has been identified as a potent oncogene as it contributes to the transcriptional activation of genes implicated in early lymphoid development. Proviral activation of Bmi-1 expression corresponds to enhanced gene-specific activation of other proto-oncogenes, including c-Myc and Pim, subsequently resulting in the progression of lymphomagenesis.