Yaf2 binds to MYC and inhibits MYC-mediated transactivation. Yaf2 also binds to MYCN and enhances MYCN-dependent transcriptional activation. Yaf2 increases calpain 2-mediated proteolysis of YY1 in vitro. Yaf2 is a component of the E2F6.com-1 complex, a repressive complex that methylates Lys-9 of histone H3, suggesting that it is involved in chromatin-remodeling.