



Chromatin -immunoprecipitation combined with ultra-high- throughput sequencing (ChIP-Seq) is revolutionizing research on gene regulation. This new technique allows for genome-wide mapping of in vivo occupied transcription factor binding sites in a quantitative manner at near-base pair resolution. Data on new transcription factors are released to the public almost every week. In most cases, computational analysis of the ChIP-Seq data has confirmed that transcription factors recognize the same DNA sequence motifs in vivo and in vitro. However, it has also become clear that only a small fraction of high-affinity sites to a transcription factors are occupied in vivo in a given cell type. Which are the additional determinants causing a transcription factors to bind to some target sites but not to others ? This is the key question addressed in this talk. Results from my group show that in vivo transcription factor binding sites are distinct from sequence-wise identical non- occupied sites in terms of cross-species conservation pattern, chromatin conformation, and flanking sequence motif content.