  Transcriptional regulation of gene expression is one of the main processes
that affect cell diversification from a single set of genes. Regulatory
proteins often interact with DNA regions located distally from the
transcription start sites (TSS) of the genes. We developed a computational
method that combines open chromatin and gene expression information for a large
number of cell types to identify these distal regulatory elements. Our method
builds correlation graphs for publicly available DNase-seq and exon array
datasets with matching samples and uses graph-based methods to filter findings
supported by multiple datasets and remove indirect interactions. The resulting
set of interactions was validated with both anecdotal information of known
long-range interactions and unbiased experimental data deduced from Hi-C and
CAGE experiments. Our results provide a novel set of high-confidence candidate
open chromatin regions involved in gene regulation, often located several Mb
away from the TSS of their target gene.
