RT Journal
A1 Heidari, Nastaran
A1 Phanstiel, Douglas H.
A1 He, Chao
A1 Grubert, Fabian
A1 Jahanbani, Fereshteh
A1 Kasowski, Maya
A1 Zhang, Michael Q.
A1 Snyder, Michael P.
T1 Genome-wide map of regulatory interactions in the human genome
JF Genome Research 
JO Genome Research 
YR 2014 
FD December 01 
VO 24 
IS 12 
SP 1905 
OP 1917 
DO 10.1101/gr.176586.114 
UL http://genome.cshlp.org/content/24/12/1905.abstract 
AB Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, GM12878) using Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) experiments targeting six broadly distributed factors. Bound regions covered 80% of DNase I hypersensitive sites including 99.7% of TSS and 98% of enhancers. Correlating this map with ChIP-seq and RNA-seq data sets revealed cohesin, CTCF, and ZNF143 as key components of three-dimensional chromatin structure and revealed how the distal chromatin state affects gene transcription. Comparison of interactions between cell types revealed that enhancer–promoter interactions were highly cell-type-specific. Construction and comparison of distal and proximal regulatory networks revealed stark differences in structure and biological function. Proximal binding events are enriched at genes with housekeeping functions, while distal binding events interact with genes involved in dynamic biological processes including response to stimulus. This study reveals new mechanistic and functional insights into regulatory region organization in the nucleus.