Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou 310058, P. R. China, Center for Bioinformatics, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, P.R. China, Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research Gatersleben (IPK), Corrensstrasse 3, D-06466 Gatersleben, Germany, The Jackson Laboratory for Genomic Medicine, and Department of Genetic and Development Biology, University of Connecticut, 400 Farmington, Connecticut 06030, USA, Department of Mathematical Sciences and School of Biological Sciences, University of Essex, Colchester, Essex CO4 3SQ, UK and Department of Computer Science, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK.
Nucleic Acids Res. 2014 Mar;42(5):3028-43. doi: 10.1093/nar/gkt1294. Epub 2013 Dec 18.
Our knowledge of the role of higher-order chromatin structures in transcription of microRNA genes (MIRs) is evolving rapidly. Here we investigate the effect of 3D architecture of chromatin on the transcriptional regulation of MIRs. We demonstrate that MIRs have transcriptional features that are similar to protein-coding genes. RNA polymerase II-associated ChIA-PET data reveal that many groups of MIRs and protein-coding genes are organized into functionally compartmentalized chromatin communities and undergo coordinated expression when their genomic loci are spatially colocated. We observe that MIRs display widespread communication in those transcriptionally active communities. Moreover, miRNA-target interactions are significantly enriched among communities with functional homogeneity while depleted from the same community from which they originated, suggesting MIRs coordinating function-related pathways at posttranscriptional level. Further investigation demonstrates the existence of spatial MIR-MIR chromatin interacting networks. We show that groups of spatially coordinated MIRs are frequently from the same family and involved in the same disease category. The spatial interaction network possesses both common and cell-specific subnetwork modules that result from the spatial organization of chromatin within different cell types. Together, our study unveils an entirely unexplored layer of MIR regulation throughout the human genome that links the spatial coordination of MIRs to their co-expression and function.
我们对高级染色质结构在 microRNA 基因（MIRs）转录中的作用的了解正在迅速发展。在这里，我们研究了染色质 3D 结构对 MIR 转录调控的影响。我们证明了 MIRs 具有与蛋白质编码基因相似的转录特征。RNA 聚合酶 II 相关的 ChIA-PET 数据表明，许多 MIRs 和蛋白质编码基因群被组织成功能分区的染色质社区，当它们的基因组位置空间上位于一起时，它们会进行协调表达。我们观察到 MIRs 在那些转录活跃的社区中表现出广泛的交流。此外，miRNA 靶相互作用在具有功能同质性的社区中显著富集，而在它们起源的相同社区中则耗尽，这表明 MIRs 在转录后水平上协调功能相关途径。进一步的研究表明存在空间 MIR-MIR 染色质相互作用网络。我们表明，空间协调的 MIR 群通常来自同一个家族，并涉及相同的疾病类别。该空间相互作用网络具有常见和细胞特异性的子网模块，这是由不同细胞类型中染色质的空间组织造成的。总之，我们的研究揭示了人类基因组中一个全新的 MIR 调控层，将 MIRs 的空间协调与它们的共表达和功能联系起来。
