Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes
Abstract The eukaryotic nucleus exhibits a highly organized 3D genome architecture, with RNA transcription and processing confined to specific nuclear structures. While intra-chromosomal interactions, such as promoter-enhancer dynamics, are well-studied, the role of inter-chromosomal interactions re...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55285-9 |
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| author | Claudia Rabuffo Markus R. Schmidt Prateek Yadav Pin Tong Roberta Carloni Anna Barcons-Simon Raúl O. Cosentino Stefan Krebs Keith R. Matthews Robin C. Allshire T. Nicolai Siegel |
| author_facet | Claudia Rabuffo Markus R. Schmidt Prateek Yadav Pin Tong Roberta Carloni Anna Barcons-Simon Raúl O. Cosentino Stefan Krebs Keith R. Matthews Robin C. Allshire T. Nicolai Siegel |
| author_sort | Claudia Rabuffo |
| collection | DOAJ |
| description | Abstract The eukaryotic nucleus exhibits a highly organized 3D genome architecture, with RNA transcription and processing confined to specific nuclear structures. While intra-chromosomal interactions, such as promoter-enhancer dynamics, are well-studied, the role of inter-chromosomal interactions remains poorly understood. Investigating these interactions in mammalian cells is challenging due to large genome sizes and the need for deep sequencing. Additionally, transcription-dependent 3D topologies in mixed cell populations further complicate analyses. To address these challenges, we used high-resolution DNA-DNA contact mapping (Micro-C) in Trypanosoma brucei, a parasite with continuous RNA polymerase II (RNAPII) transcription and polycistronic transcription units (PTUs). With approximately 300 transcription start sites (TSSs), this genome organization simplifies data interpretation. To minimize scaffolding artifacts, we also generated a highly contiguous phased genome assembly using ultra-long sequencing reads. Our Micro-C analysis revealed an intricate 3D genome organization. While the T. brucei genome displays features resembling chromosome territories, its chromosomes are arranged around polymerase-specific transcription hubs. RNAPI-transcribed genes cluster, as expected from their localization to the nucleolus. However, we also found that RNAPII TSSs form distinct inter-chromosomal transcription hubs with other RNAPII TSSs. These findings highlight the evolutionary significance of inter-chromosomal transcription hubs and provide new insights into genome organization in T. brucei. |
| format | Article |
| id | doaj-art-5a1f74b1ec8c4dfea33e4674c18adcdd |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-5a1f74b1ec8c4dfea33e4674c18adcdd2025-08-20T02:43:33ZengNature PortfolioNature Communications2041-17232024-12-0115111810.1038/s41467-024-55285-9Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomesClaudia Rabuffo0Markus R. Schmidt1Prateek Yadav2Pin Tong3Roberta Carloni4Anna Barcons-Simon5Raúl O. Cosentino6Stefan Krebs7Keith R. Matthews8Robin C. Allshire9T. Nicolai Siegel10Division of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität MünchenDivision of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität MünchenDivision of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität MünchenWellcome Centre for Cell Biology, School of Biological Sciences, University of EdinburghWellcome Centre for Cell Biology, School of Biological Sciences, University of EdinburghDivision of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität MünchenDivision of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität MünchenGene Center and Department of Biochemistry, Ludwig-Maximilians-Universität MünchenInstitute of Immunology and Infection Research, University of EdinburghWellcome Centre for Cell Biology, School of Biological Sciences, University of EdinburghDivision of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität MünchenAbstract The eukaryotic nucleus exhibits a highly organized 3D genome architecture, with RNA transcription and processing confined to specific nuclear structures. While intra-chromosomal interactions, such as promoter-enhancer dynamics, are well-studied, the role of inter-chromosomal interactions remains poorly understood. Investigating these interactions in mammalian cells is challenging due to large genome sizes and the need for deep sequencing. Additionally, transcription-dependent 3D topologies in mixed cell populations further complicate analyses. To address these challenges, we used high-resolution DNA-DNA contact mapping (Micro-C) in Trypanosoma brucei, a parasite with continuous RNA polymerase II (RNAPII) transcription and polycistronic transcription units (PTUs). With approximately 300 transcription start sites (TSSs), this genome organization simplifies data interpretation. To minimize scaffolding artifacts, we also generated a highly contiguous phased genome assembly using ultra-long sequencing reads. Our Micro-C analysis revealed an intricate 3D genome organization. While the T. brucei genome displays features resembling chromosome territories, its chromosomes are arranged around polymerase-specific transcription hubs. RNAPI-transcribed genes cluster, as expected from their localization to the nucleolus. However, we also found that RNAPII TSSs form distinct inter-chromosomal transcription hubs with other RNAPII TSSs. These findings highlight the evolutionary significance of inter-chromosomal transcription hubs and provide new insights into genome organization in T. brucei.https://doi.org/10.1038/s41467-024-55285-9 |
| spellingShingle | Claudia Rabuffo Markus R. Schmidt Prateek Yadav Pin Tong Roberta Carloni Anna Barcons-Simon Raúl O. Cosentino Stefan Krebs Keith R. Matthews Robin C. Allshire T. Nicolai Siegel Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes Nature Communications |
| title | Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes |
| title_full | Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes |
| title_fullStr | Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes |
| title_full_unstemmed | Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes |
| title_short | Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes |
| title_sort | inter chromosomal transcription hubs shape the 3d genome architecture of african trypanosomes |
| url | https://doi.org/10.1038/s41467-024-55285-9 |
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