Cooperative binding of transcription factors in the human genome.

Transcription factors (TFs) cooperatively bind to specific DNA sequences to control chromatin and gene transcription in eukaryotes. Here, we searched canonical binding, co-binding and tethered binding regions of a TF within ChIP-seq peaks, and investigated the effect of TF-TF cooperation in human GM12878 and K562 cells. We found that TFs except for CTCF and SPI1 showed a large proportion of co-binding and tethered binding regions, and TFs frequently co-binding with other TFs would also frequently tether other TFs to their binding positions. We further observed lower in vivo nucleosome occupancy, higher in vitro nucleosome occupancy and higher levels of H2A.Z, H3K27ac, H3K9ac, H3K4me1, H3K4me2 and H3K4me3 within distal co-binding regions where other TFs were recruited. In addition, target genes for proximal co-binding regions where other TFs were recruited showed significantly higher expression levels. These results indicated that TF-TF cooperation directly associates with the chromatin structure and gene transcription.