Speaker
Description
Cell differentiation towards neurons undergoes global changes in three-dimensional (3D) genome organization and gene expression. Our integration of multi-omic data generated in the frame of the Functional ANnoTation Of the Mammalian genome (FANTOM6) to chart interplay of between RNA-DNA and DNA-DNA interactions in the nucleus during in vitro differentiation of human induced pluripotent stem cells to cortical neurons finds a group of intronic RNAs engages in chromatin contacts with distal loci on the same or on different chromosomes. We detect such trans-contacting intronic RNAs (TIRs) in all cell types profiled by FANTOM6, but most prominently in neurons, where TIRs are produced from highly expressed, neuron-specific, long (mean length: 400 kilobases, kb) protein-coding genes. In neurons, TIRs accumulate in the nucleus forming large clouds around their source loci, and they occasionally spread across the nucleus. Notably, knockdown of a single TIR by antisense oligonucleotides leads to downregulation of multiple genes implicated in NDDs and most other TIRs. We propose that TIRs orchestrate cell type-specific gene expression during neurodifferentiation and might be pathogenically linked to NDD
| Author(s) | Wenjing Kang*1,2, Wing Hin Yip1,2, Quentin Verron1,2, Britta A.M. Bouwman1,2, Xiaoze Li-Wang1,2, Andrea Abou Yaghi1,2, Mitsuyoshi Murata3, Merula Stout1,2, Lorenzo Salviati4, Xufeng Shu3, Kayoko Yasuzawa3, Marco Gaviraghi4, Rodrigo Pracana4, Johan Lord1,2, Roberto Ballarino1,2, Anna Falk5,6, Jay W. Shin3,7, Takeya Kasukawa3, Chi Wai Yip3, Masaki Kato3, Hazuki Takahashi3, Nicola Crosetto1,2,4, Piero Carninci3,4, Magda Bienko1,2,4 |
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| Affiliation(s) | 1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden 2 Science for Life Laboratory, Stockholm, Sweden 3 RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045 Japan 4 Human Technopole, Milan, Italy 5 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden 6 Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, Lund, Sweden 7 Genome Institute of Singapore, A*STAR Singapore 138672, Singapore |
