Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation

• Main Authors: 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, Cheung, Edwin, Liu, Edison, Sung, Wing-Kin, Snyder, Michael, Ruan, Yijun, Fullwood, Melissa Jane
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2013
• Subjects: DRNTU::Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/99700; http://hdl.handle.net/10220/10795
• Institution: Nanyang Technological University

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.