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 repressed in G0/early G1 through a binding site for the transcription factor E2F. Here, we show that the B-myb repressor element is specifically recognised by heterodimers consisting of DP-1 and E2F-1, E2F-3 or E2F-4. Surprisingly, E2F-mediated repression is dependent on a contiguous corepressor element that resembles the CHR previously established as a corepressor of the CDE in cell cycle genes derepressed in S/G2, 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 interact with the minor groove, as previously shown by in vivo footprinting for the cyclin A CHR. The B-myb and cdc25C CHRs are related with respect to protein binding but are functionally clearly distinct. Our results support a model where both E2F- and CDE-mediated repression, acting at different stages in the cell cycle, are dependent on promoter-specific CHR elements.
Liu
N
N
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, Germany.
Lucibello
F C
FC
Zwicker
J
J
Engeland
K
K
Müller
R
R
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; D050704:E2F4 Transcription Factor; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D056465:Retinoblastoma-Binding Protein 1; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050699:E2F3 Transcription Factor; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; C493754:E2f1 protein, mouse; C493763:E2f4 protein, mouse; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; D056465:Retinoblastoma-Binding Protein 1; C493735:TFDP1 protein, human; C493736:Tfdp1 protein, mouse; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; D008156:Luciferases