Genome-wide map of regulatory interactions in the human genome.

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.

journal_name

Genome Res

journal_title

Genome research

authors

Heidari N,Phanstiel DH,He C,Grubert F,Jahanbani F,Kasowski M,Zhang MQ,Snyder MP

doi

10.1101/gr.176586.114

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

1905-17

issue

12

eissn

1088-9051

issn

1549-5469

pii

gr.176586.114

journal_volume

24

pub_type

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