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

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• 作者：Guoliang Li¹ ; ¹⁰ ; Xiaoan Ruan¹ ; ¹⁰ ; Raymond  ; K. Auerbach² ; ¹⁰ ; Kuljeet  ; Singh Sandhu¹ ; ¹⁰ ; Meizhen Zheng¹ ; Ping Wang¹ ; Huay  ; Mei Poh¹ ; Yufen Goh¹ ; Joanne Lim¹ ; Jingyao Zhang¹ ; Hui  ; Shan Sim¹ ; Su  ; Qin Peh¹ ; Fabianus  ; Hendriyan Mulawadi¹ ; Chin  ; Thing Ong¹ ; Yuriy  ; L. Orlov¹ ; Shuzhen Hong¹ ; Zhizhuo Zhang³ ; Steve Landt⁴ ; Debasish Raha⁴ ; Ghia Euskirchen⁴ ; Chia-Lin Wei¹ ; Weihong Ge⁵ ; Huaien Wang⁶ ; Carrie Davis⁶ ; Katherine I. Fisher-Aylor⁷ ; Ali Mortazavi⁷ ; Mark Gerstein² ; Thomas Gingeras⁶ ; Barbara Wold⁷ ; Yi Sun⁵ ; Melissa  ; J. Fullwood¹ ; Edwin Cheung¹ ; ⁸ ; Edison Liu¹ ; Wing-Kin Sung¹ ; ³ ; Michael Snyder⁴ ; ^{mpsnyder@stanford.edu} ; Yijun Ruan¹ ; ⁹ ; ^{ruanyj@gis.a-star.edu.sg}
• 刊名：Cell
• 出版年：2012
• 出版时间：20 January 2012
• 年：2012
• 卷：148
• 期：1-2
• 页码：84-98
• 全文大小：2753 K

文摘

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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.