Fc. Lucibello et al., THE DIFFERENTIAL BINDING OF E2F AND CDF REPRESSOR COMPLEXES CONTRIBUTES TO THE TIMING OF CELL-CYCLE-REGULATED TRANSCRIPTION, Nucleic acids research, 25(24), 1997, pp. 4921-4925
B-myb and cdc25C exemplify different groups of genes whose transcripti
on is consecutively up-regulated during the cell cycle, Both promoters
are controlled by transcriptional repression via modules consisting o
f 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, wh
ich is derepressed early (mid G(1)), is preferentially recognized by E
2F-DP complexes and that a mutation selectively abolishing E2F binding
impairs regulation, In contrast, the cdc25C repressor module, which i
s derepressed late (S/G(2)), interacts selectively with CDE-CHR bindin
g factor-1 (CDF-1), E2F binding, but not CDF-1 binding, requires speci
fic 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 re
sults in up-regulation in rate G(1), 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 repre
ssor complexes contributes to the timing of promoter activity during t
he cell cycle.