Details

Autor(en) / Beteiligte

• 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
• Ruan, Yijun

Titel

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

Ist Teil von

• Cell, 2012-01, Vol.148 (1-2), p.84-98

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. [Display omitted] ► Promoter-centered interactions are complex and widespread ► Higher-order chromatin architectures facilitate active and coordinated transcription ► Interacting promoters possess combinatorial regulatory functions ► Large enhancer-promoter repertoire allows functional annotation of noncoding elements Higher order chromatin interactions between promoters synergistically promote transcription of clustered genes. These interactions indicate a topological, combinatorial mechanism of transcriptional and also suggest functions for noncoding elements, including those associated with disease, by connecting them to target genes.