It is currently unclear how these differences in expression arise between genes, however we suggest that they reside in subtle differences in their promoter structure.
The increased sensitivity of such approaches make them more capable of measuring subtle differences in OAS1 promoter activity that may be important for inhibiting viral replication during the initial stage of infection.
Under such conditions, the use of a luciferase reporter assay, which requires sufficient treatment times to allow for translation and accumulation of firefly luciferase, may not accurately depict the subtle changes at individual promoters at shorter time points.
This signal was best observed in upregulation and cell cycle gene sets (Figure 6Cand E), yet subtle enrichment in transgenic promoters could also be detected in specific downregulation (Figure 6B) and specific upregulation, where the FREAC2 motif ranked among the top 15 PWMs (Table S4).
More recently, a quantitative thermodynamic analysis of the interaction between CSL and the two individual CSL binding sites in the HES-1 promoter have revealed subtle differences in the binding affinities of CSL for each DNA binding site [13].
Whist dramatic switching on or off facilitated by DNA methylation may occur within these promoter regions, more subtle and perhaps dynamic effects may however be missed that are occurring in the surrounding CGI shores (regions within 2 kb of the islands) [ 44].
This is significant because it emphasizes that the subtle difference in signaling due to promoter polymorphisms can alter the course of biochemical pathway resulting in variation in disease phenotype.
