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 Resjournal_title
Genome researchauthors
Heidari N,Phanstiel DH,He C,Grubert F,Jahanbani F,Kasowski M,Zhang MQ,Snyder MPdoi
10.1101/gr.176586.114subject
Has Abstractpub_date
2014-12-01 00:00:00pages
1905-17issue
12eissn
1088-9051issn
1549-5469pii
gr.176586.114journal_volume
24pub_type
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