Polycomb (Pc) is involved in the stable and heritable repression of homeotic gene activity during Drosophila development. Here, we report the identification of a novel human Pc homolog, hPc2. This gene is more closely related to a Xenopus Pc homolog, XPc, than to a previously described human Pc homolog, CBX2 (hPc1). However, the hPc2 and CBX2/hPc1 proteins colocalize in interphase nuclei of human U-2 OS osteosarcoma cells, suggesting that the proteins are part of a common protein complex. To study the functions of the novel human Pc homolog, we generated a mutant protein, ⌬hPc2, which lacks an evolutionarily conserved C-terminal domain. This C-terminal domain is important for hPc2 function, since the ⌬hPc2 mutant protein which lacks the C-terminal domain is unable to repress gene activity. Expression of the ⌬hPc2 protein, but not of the wild-type hPc2 protein, results in cellular transformation of mammalian cell lines as judged by phenotypic changes, altered marker gene expression, and anchorage-independent growth. Specifically in ⌬hPc2-transformed cells, the expression of the c-myc proto-oncogene is strongly enhanced and serum deprivation results in apoptosis. In contrast, overexpression of the wild-type hPc2 protein results in decreased c-myc expression. Our data suggest that hPc2 is a repressor of proto-oncogene activity and that interference with hPc2 function can lead to derepression of proto-oncogene transcription and subsequently to cellular transformation.

BS69 was ®rst identi®ed as a protein that interacts directly with the transactivation domain (conserved region 3) of the 289R adenovirus type 5 E1A protein.We show here that BS69 is a potent repressor of transcription. BS69 mediates repression, at least in part, through interaction with the co-repressor N-CoR. BS69 interacts with N-CoR through a MYND domain in its carboxyl terminus. A recently cloned splice variant of BS69, designated BRAM1, is also capable of interacting with N-CoR and E1A, but unlike BS69, is not able to repress transcription, indicating that N-CoR interaction is necessary but not su cient for BS69 repression. Expression of E1A inhibits repression mediated by BS69. Our data suggest that BS69 participates in transcriptional repressor complexes and that E1A can modulate these complexes through interaction with BS69. Oncogene (2000) 19, 1538 ± 1546.

B-myb, a ubiquitously expressed member of the myb gene family, is highly regulated throughout the cell cycle and appears to be required for cell cycle progression. In contrast to its relatives A-myb, c-myb, and v-myb, no transforming activity of B-myb has been reported thus far. We report here that B-myb can rescue senescence induced by an activated ras oncogene in rodent cells in vitro. We show that transformation by B-Myb involves its ability to activate transcription. Similar to other oncogenic transcription factors, such as c-Myc and E2F, we show that B-Myb also has repression activity. We demonstrate that the Cterminus of B-Myb can function as a repressor of transcription, that B-Myb interacts with the repressor molecules BS69 and NCoR and that the repression function, like the transactivation domain, contributes to B-myb transformation. q