Title

Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation.

Document Type

Article

Publication Date

1-20-2012

Keywords

Cell Line, Tumor, Chromatin, Chromatin Immunoprecipitation, Enhancer Elements, Genetic, Gene Expression Regulation, Genome-Wide Association Study, Humans, Promoter Regions, Genetic, RNA Polymerase II, Transcription, Genetic

JAX Source

Cell 2012 Jan 20; 148(1-2):84-98.

PMID

22265404

Abstract

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells.