Detecting cooperatively bound transcription factor pairs through ChIP-seq


Vishaka Datta, NCBS Bangalore

The transcription of many eukaryotic genes is regulated by the binding of multiple transcription factors (TFs) within short distances of each other. In such regions, the binding of one TF can increase the DNA binding affinity of an adjacent TF. This increase in affinity is referred to as cooperativity. Current bioinformatics methods only detect a small fraction of cooperative binding events, owing to their restrictive underlying assumptions. Thus, it is unclear as to how frequently any given pair of TFs can cooperatively bind DNA. The influence of these interactions on TF-DNA binding can be understood through data from high throughput sequencing techniques such as ChIP-seq. These methods give a list of genomic locations bound by a pair of TFs in vivo, as well as a (noisy) measure of their binding affinities at each location. We propose a method that can find those locations where the a pair of TFs interacted while binding DNA. The highlight of this method is that it uses only the binding affinities of each TF for detecting interactions while not taking the underlying sequence that is bound into consideration.