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

Li, G., Ruan, X. A., Auerbach, R. K., Sandhu, K. S., Zheng, M., Wang, P. C., Poh, H. M., Goh, Y., Lim, J., Zhang, J., Sim, H. S., Peh, S. Q., Mulawadi, F. H., Ong, C. T., Orlov, Y. L., Hong, S., Zhang, Z., Landt, S. G., Raha, D., Euskirchen, G., Wei, C-L., Ge, W., Wang, H., Davis, C. A., Fisher-Aylor, K. I., Mortazavi, A., Gerstein, M., Gingeras, T. R., Wold, B., Sun, Yi, Fullwood, M. J., Cheung, E., Liu, E., Sung, W.-K., Snyder, M., Ruan, Y. (2012) Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation. Cell, 148 (1–2). pp. 84-98. ISSN 0092-8674

URL: http://www.ncbi.nlm.nih.gov/pubmed/22265404
DOI: 10.1016/j.cell.2011.12.014

Abstract

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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > annotation > map annotation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL labs > Gingeras lab
CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service
Depositing User: CSHL Librarian
Date Deposited: 08 Mar 2012 14:22
Last Modified: 30 Oct 2015 16:40
PMCID: PMC3339270
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25353

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