CELL-CYCLE-REGULATED REPRESSION OF B-MYB TRANSCRIPTION - COOPERATION OF AN E2F SITE WITH A CONTIGUOUS COREPRESSOR ELEMENT

B-myb belongs to a group of cell cycle genes whose transcription is re pressed in G(0)/early G(1) through a binding site for the transcriptio n factor E2F. Here, we show that the B-myb repressor element is specif ically recognised by heterodimers consisting of DP-1 and E2F-1, E2F-3 or E2F-4. Surprisingly, EPF-mediated repression is dependent on a cont iguous compressor element that resembles the CHR previously establishe d as a compressor of the CDE in cell cycle genes derepressed in S/G(2) , such as cyclin A, cdc2 and cdc25C. A factor binding to the B-myb CHR was identified in fractionated HeLa nuclear extract and found to inte ract with the minor groove, as previously shown by in vivo footprintin g for the cyclin A CHR. The B-myb and cdc25C CHRs are related with res pect to protein binding but are functionally clearly distinct. Our res ults support a model where both E2F- and CDE-mediated repression, acti ng at different stages in the cell cycle, are dependent on promoter-sp ecific CHR elements.