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Advances in the methods for detecting protein-DNA interactions have played a key role in determining the directions of research into the mechanisms of transcriptional regulation. The most recent major technological transformation happened a decade ago, with the move from using tiling arrays [chromatin immunoprecipitation (ChIP)-on-Chip] to high-throughput sequencing (ChIP-seq) as a readout for ChIP assays. In addition to the numerous other ways in which it is superior to arrays, by eliminating the need to design and manufacture them, sequencing also opened the door to carrying out comparative analyses of genome-wide transcription factor occupancy across species and studying chromatin biology in previously less accessible model and nonmodel organisms, thus allowing us to understand the evolution and diversity of regulatory mechanisms in unprecedented detail. Here, we review the biological insights obtained from such studies in recent years and discuss anticipated future developments in the field.

ChIP-ping the branches of the tree: functional genomics and the evolution of eukaryotic gene regulation