The 38 genes with their putative promoters affected were listed in Additional file 7.
Considering the findings of Jensen and Hammer (1998b) and Rud et al. (2006) [ 13, 15] these classes are: 1) promoters affected in their spacer size, 2) promoters affected in their -35 or -10 box, 3) promoters affected both in their spacer size and in their -35 or -10 box, and 4) no apparent anomalies in their sequence.
We found that there were a total of 127 downstream promoters affected by E2 treatment, while only 87 upstream promoters were affected – a significant bias (p = 0.00625 in a chi-squared test).
To test whether methylation of candidate gene promoters affects the expression of corresponding genes, we analyzed mRNA expression levels in parental and MMO cells.
The results show that transcription from different promoters affects the activity of enhancers, counteracting their ability to activate the target genes.
We identified a distinct set of promoters affected even by subtle inhibition of the Ras-ERK and phosphatidylinositol-3-kinase-Akt signal-transduction pathways.
The identification of promoters affecting the transition rate between the PCDP and the CP leading to interval cancer with rapid progression has an important role in personalised treatment and therapy (Dowsett and Dunbier, 2008).
These results suggested that the competition for a regulatory protein among its binding sites on the promoters affects oscillation bifurcation, similar to the effect caused by an increase in the number of decoy sites in a genetic circuit [ 6].
We proposed an individual-risk-score-based approach that translates state-of-the-art scientific evidence into the initiators and promoters affecting onset and subsequent progression of breast tumour underpinning a novel multi-variable three-state temporal natural history model.
