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Fine-tuning of transcription factor binding

Many transcription factors bind to regulatory genomic regions through the recognition of specific DNA sequences. Eran Segal and colleagues developed a new high-throughput method, termed BunDLE-seq (Binding to Designed Library, Extracting and Sequencing), that quantitatively measures transcription factor binding to thousands of 200-bp sequences in a single experimental assay (Genome Res. doi:10.1101/gr.185033.114; 11 March 2015). As proof of principle, they studied the binding dynamics of two yeast transcription factors, Gal4 and Gcn4. Interestingly, their data indicate that sequence variation flanking the core transcription factor binding site has a significant impact on binding. They also investigated the role of transcription factor concentration and the number and position of binding sites in events involving single or multiple transcription factors. This method, combined with cell type–specific epigenetic information, could have the potential to elucidate transcriptional mechanisms that contribute to the differential regulation of transcription factor target loci. It will be interesting to perform detailed comparisons of BunDLE-seq and ChIP-seq profiles and to test combinations of different transcription factors and other chromatin-binding proteins.

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Faial, T. Fine-tuning of transcription factor binding. Nat Genet 47, 429 (2015). https://doi.org/10.1038/ng.3297

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