Genome-Wide Assessment Of The Binding Effects Of Artificial Transcriptional Activators By Utilizing The Power Of High-Throughput Sequencing

One of the major goals in DNA-based personalized medicine is the development of sequence-specific small molecules to target the genome by means of synthetic biology; SAHA-PIPs belong to such class of small molecules. In a complex eukaryotic genome, the differential biological effects of SAHA-PIPs remain unclear. These questions can be addressed by directly identifying the binding regions of small molecules across the genome; however, it is a challenge to enrich specifically the small-molecule-bound DNA without chemical cross-linking. Here, we developed a method using high-throughput sequencing to map the binding area of non-cross-linked small molecules throughout the chromatinized human genome. Analysis of the sequenced data confirmed the presence of specific binding sites for SAHA-PIPs among the enriched sequence reads. Mapping the binding sites and enriched regions on the human genome clarifies the origin of the distinctive biological effects of SAHA-PIP. This approach will be useful for identifying the functionality of other small molecules on a large scale.