Regulation of the beta1,4-Galactosyltransferase I promoter by E2F1.

Cell surface carbohydrate chains are widely known to contribute to cell migration, recognition and proliferation. beta1,4-Galactosyltransferase I (beta1,4GalT I) transfers galactose to the terminal N-acetylglucosamine of complex-type N-glycan, and contributes to cell proliferation, differentiation and migration. Here, we identified beta1,4GalT I as a novel target gene of cell cycle regulator E2F1. E2F1 proteins interact with the promoter of the beta1,4GalT I gene in vivo, and E2F1 over-expression stimulates the activity of beta1,4GalT I promoter and the mRNA and protein expression of beta1,4GalT I, and augments the level of beta1, 4-galactosyltion. Site-specific mutagenesis revealed that this region which contains two E2F1 binding site (nt -215 to -207 and +1 to +6) is necessary for beta1,4GalT I activation by E2F1. Furthermore, down-regulation of beta1,4GalT I expression attenuates E2F1-induced DNA synthesis and cell cycle progression as well as the expression of cell-cycle regulator Cyclin D1. Thus, beta1,4GalT I is an important E2F1 target gene that is required for cell cycle progression in mammalian cells, which elicits a new mechanism of cell growth and a new mechanism of beta1,4GalT I transcription.