Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation.
Cell Line, Tumor, Chromatin, Chromatin Immunoprecipitation, Enhancer Elements, Genetic, Gene Expression Regulation, Genome-Wide Association Study, Humans, Promoter Regions, Genetic, RNA Polymerase II, Transcription, Genetic
Cell 2012 Jan 20; 148(1-2):84-98.
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.
Li, Guoliang; Ruan, Xiaoan; Auerbach, Raymond K; Sandhu, Kuljeet Singh; Zheng, Meizhen; Wang, Ping; Poh, Huay Mei; Goh, Yufen; Lim, Joanne; Zhang, Jingyao; Sim, Hui Shan; Peh, Su Qin; Mulawadi, Fabianus Hendriyan; Ong, Chin Thing; Orlov, Yuriy L; Hong, Shuzhen; Zhang, Zhizhuo; Landt, Steve; Raha, Debasish; Euskirchen, Ghia; Wei, Chia-Lin; Ge, Weihong; Wang, Huaien; Davis, Carrie; Fisher-Aylor, Katherine I; Mortazavi, Ali; Gerstein, Mark; Gingeras, Thomas; Wold, Barbara; Sun, Yi; Fullwood, Melissa J; Cheung, Edwin; Liu, Edison; Sung, Wing-Kin; Snyder, Michael; and Ruan, Yijun, "Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation." (2012). Faculty Research 2012. 119.