title: Dissecting the chromatin interactome of microRNA genes.
abstract: 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.
authors.affiliation: 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.
authors.forename: Dijun
authors.initials: D
authors.lastname: Chen
authors.forename: Liang-Yu
authors.initials: LY
authors.lastname: Fu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Harrison
authors.forename: Hugh P
authors.initials: HP
authors.lastname: Shanahan
authors.forename: Christian
authors.initials: C
authors.lastname: Klukas
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D035683:MicroRNAs