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

Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation
Title:
Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation
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Cell
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Publication Date:
20 January 2012
Citation:
Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation Guoliang Li, Xiaoan Ruan, Raymond K. Auerbach, Kuljeet Singh Sandhu, Meizhen Zheng, Ping Wang, Huay Mei Poh, Yufen Goh, Joanne Lim, Jingyao Zhang, Hui Shan Sim, Su Qin Peh, Fabianus Hendriyan Mulawadi, Chin Thing Ong, Yuriy L. Orlov, Shuzhen Hong, Zhizhuo Zhang, Steve Landt, Debasish Raha, Ghia Euskirchen, Chia-Lin Wei, Weihong Ge, Huaien Wang, Carrie Davis, Katherine I. Fisher-Aylor, Ali Mortazavi, Mark Gerstein, Thomas Gingeras, Barbara Wold, Yi Sun, Melissa J. Fullwood, Edwin Cheung, Edison Liu, Wing-Kin Sung, Michael Snyder, Yijun Ruan Cell - 20 January 2012 (Vol. 148, Issue 1, pp. 84-98)
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.
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ISSN:
0092-8674
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