Genome Institute of Singapore, Singapore 138672, Republic of Singapore.
Cell. 2012 Jan 20;148(1-2):84-98. doi: 10.1016/j.cell.2011.12.014.
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.
高等真核生物的染色体结构对转录调控的影响仍知之甚少。通过使用全基因组染色质互作分析与 Paired-End-Tag 测序（ChIA-PET），我们在人类细胞中绘制了与 RNA 聚合酶 II 相关的长程染色质互作图谱，揭示了广泛存在的启动子为中心的基因内、基因间和基因间的相互作用。这些相互作用进一步聚集为更高阶的簇，其中近端和远端基因通过启动子-启动子相互作用连接。大多数具有启动子-启动子相互作用的基因是活跃的并协同转录，一些相互作用的启动子可以相互影响，这暗示了转录调控的组合复杂性。对不同细胞系的比较分析表明，细胞特异性染色质相互作用可以为细胞特异性转录提供结构框架，并表明增强子-启动子相互作用对于细胞特异性功能有显著富集。此外，通过遗传鉴定的疾病相关非编码元件被发现通过长程相互作用与相应的基因空间连接。总的来说，我们的研究为人类细胞中管家基因和细胞特异性基因的三维染色质相互作用的转录调控提供了新的见解。
