Genome-wide map of regulatory interactions in the human genome

Genome Res. 2014 Dec;24(12):1905-17. doi: 10.1101/gr.176586.114. Epub 2014 Sep 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCCTC-Binding Factor
  • Cell Cycle Proteins / genetics
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosome Mapping*
  • Cluster Analysis
  • Computational Biology
  • Datasets as Topic
  • Enhancer Elements, Genetic
  • Epistasis, Genetic*
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genetic Loci
  • Genome, Human*
  • Genome-Wide Association Study*
  • Genomics / methods
  • Humans
  • Organ Specificity / genetics
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid*
  • Repressor Proteins / genetics
  • Trans-Activators / genetics
  • Transcription Factors / metabolism

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • ZNF143 protein, human
  • cohesins

Associated data

  • GEO/GSE59395