These putative enhancers are associated with increased gene expression of neighbouring genes and significantly enriched in multiple TF bound loci in agreement with combinatorial models of TF binding.
Available evidence, however, suggests that TFs and their targets display a many-to-many relationship: thus, multiple TFs bind to a promoter while individual TFs control multiple genes.
In that study, the authors analyzed AS of 24 TFs and found that when multiple TFs bind to the same SNP, they frequently bind to the same allele.
Multiple TFs bind to the region and the SNP shows allelic differences in enhancer activity in pancreatic islet cells (46), highlighting its potential importance in T2D pathogenesis.
Transcript levels are in part determined by the combinatorial and overlapping functions of multiple transcription factors (TFs) bound to gene promoters.
A classic example is the interferon-beta enhanceosome, in which multiple transcription factors (TFs) bind overlapping and adjacent transcription factor binding sites (TFBS) (Panne et al. 2004, 2007).
Only genes with at least 2 TFs bound were used for this analysis since genes bound by 1 TF are not suitable for testing interactions.
Adding multiple copies of an operator site will permit multiple TFs to bind to a single promoter and may therefore increase maximal activation or repression levels, leading to upward vertical extension or less leakage, respectively.
Recently, protein binding microarray experiments have shown that the sequence variety and position-interdependence between bases in sequence motifs are even higher than previously expected, and that TFs bind a rich spectrum of k-mers not fully captured even by multiple PWMs [7].
In contrast, even though stress-related TFs bind the robust gene, its transcriptional programs might not be altered unless multiple originally bound TFs are bypassed.
