The differential binding of E2F and CDF repressor complexes contributes to the timing of cell cycle-regulated transcription.
B- myb and cdc25C exemplify different groups of genes whose transcription is consecutively up-regulated during the cell cycle. Both promoters are controlled by transcriptional repression via modules consisting of an E2F binding site (E2FBS) or the related CDE plus a contiguous CHR co-repressor element. We now show that the B- myb repressor module, which is derepressed early (mid G1), is preferentially recognized by E2F-DP complexes and that a mutation selectively abolishing E2F binding impairs regulation. In contrast, the cdc25C repressor module, which is derepressed late (S/G2), interacts selectively with CDE-CHR binding factor-1 (CDF-1). E2F binding, but not CDF-1 binding, requires specific nucleotides flanking the E2FBS/CDE core, while CDF-1 binding, but not E2F binding, depends on specific nucleotides in the CHR. Swapping these nucleotides between the two promoters profoundly changes protein binding patterns and alters expression kinetics. Thus predominant CDF-1 binding leads to derepression in late S, predominant E2F binding results in up-regulation in late G1, while promoters binding both E2F and CDF-1 with high efficiency show intermediate kinetics. Our results support a model where the differential binding of E2F and CDF-1 repressor complexes contributes to the timing of promoter activity during the cell cycle.
Lucibello
F C
FC
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, Emil-Mannkopff-Strasse 2, D-35033 Marburg, Germany.
Liu
N
N
Zwicker
J
J
Gross
C
C
Müller
R
R
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors; D005786:Gene Expression Regulation / Q000502:physiology*; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D046911:Macromolecular Substances; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors