The ftn mRNA expression levels were down-regulated 4- to 20-fold in the SO2426 null mutant across the entire temporal range, with the peak in repression occurring at the 180-min time point (Table 1).
Although this activity occurs at the LAT2 gene [ 47] and only on a subset of our ChIP-seq peaks, the repression characterized by local alterations in H3K27me3 is likely not the dominant mechanism in Kasumi-1 cells.
This result is in agreement with earlier studies [ 5, 6], and demonstrates that the temporarily confined expression patterns of meiotically regulated genes enables association of peak expression or repression with a specific developmental stage in our experimental setup.
Interestingly, the 244 RefSeq ncRNAs showed a similar expression pattern as the protein coding genes, where peak expression or repression levels were observed at 1.5 and 24 hr post stimulation.
Although it is known that oscillation frequency can manifest spatially, for example by determining somite length in vertebrate embryos [ 28, 29], this model temporally links the onset, peak, and then repression of transcription to signal frequency, providing a timing mechanism to induce gene expression at the correct point in development.
To illustrate the dose-dependent response of certain genes to either MMS or γ-ray, six smaller clusters from Figure 5 in which one of three specific dose-dependent responses was observed: monotonically increasing, monotonically decreasing, or biphasic (where peak induction or repression occurred at the intermediate dose) were identified and are presented in Figure 6.
The high overall flexibility of the nucleoprotein assembly is reflected in the decay of repression peaks with operator spacings above 70 bp.
In the case of the Müller et al. data set, our computed repression peaks are somewhat broader than the corresponding experimental ones (see Figure 5A).
Compared with the Müller et al. results, Becker et al.'s enhanced-repression values are significantly greater (about three-fold as judged by the repression peaks), whereas the amplitude of the helical dependence is about two-fold smaller.
But it was under Gen. Sani Abacha, Nigeria's military ruler from 1993 to 1998, that the repression reached its peak.
In particular, our model explains the optimal O1 O3 separation of 92 bp observed in the wild-type operon, which coincides with a strong peak in the enhanced- repression curve (Figure 5A).
