Research Article Integration of 198 ChIP-seq Datasets Reveals Human

We analyzed 198 datasets of chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) and developed a methodology for identification of high-confidence enhancer and promoter regions from transcription factor ChIP-seq data alone. We identify 32,467 genomic regions marked with ChIP-seq binding peaks in 15 or more experiments as high-confidence cis-regulatory regions. Although the selected re-gions mark only *0.67 % of the genome, 70.5 % of our predicted binding regions fall within independently identified, strongly expression-correlated and histone-marked en-hancer regions, which cover *8 % of the genome (Ernst et al., Nature 2011, 473, 43–49). Even more remarkably, 85.6 % of our selected regions overlap transcription factor (TF) binding regions identified in evolutionarily conserved DNase1 hypersensitivity cluster regions, which cover 0.75 % of the genome (Boyle et al., Genome Research 2011, 21, 456– 464). P-values for these overlaps are effectively zero (Z-scores of 328 and 715 re-spectively). Furthermore, 62 % of our selected regions overlap the intersection of the evolutionarily conserved DNase1 hypersensitivity-identified TF-binding regions of Boyle et al. (2011) with the histone-marked enhancers found to be strongly associated with transcriptional activity by Ernst et al. (2011). Two hundred thirty of our candidate cis-regulatory regions overlap cancer-associated variants reported in the Catalogue of Somatic Mutations in Cance