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Published January 20, 2012 | Supplemental Material + Accepted Version
Journal Article Open

Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation


Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIAPET), 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.

Additional Information

© 2012 Elsevier Inc. Received 18 July 2011. Revised 21 October 2011. Accepted 12 December 2011. Available online 19 January 2012. Published: January 19, 2012. We acknowledge the Genome Technology and Biology Group at the Genome Institute of Singapore for technical support. This work was supported by Singapore A*STAR and an NIH grant (HG004456) to Y.R.

Attached Files

Accepted Version - nihms345629.pdf

Supplemental Material - mmc1.pdf

Supplemental Material - mmc2.xls

Supplemental Material - mmc3.xls

Supplemental Material - mmc4.xls


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