Cell
Volume 148, Issues 1–2, 20 January 2012, Pages 84-98
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Article
Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation

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Summary

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.

Highlights

► Promoter-centered interactions are complex and widespread ► Higher-order chromatin architectures facilitate active and coordinated transcription ► Interacting promoters possess combinatorial regulatory functions ► Large enhancer-promoter repertoire allows functional annotation of noncoding elements

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These authors contributed equally to this work