4.8 Article

Spatial organization of transcribed eukaryotic genes

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NATURE CELL BIOLOGY
卷 24, 期 3, 页码 327-+

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NATURE PORTFOLIO
DOI: 10.1038/s41556-022-00847-6

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  1. Deutsche Forschungsgemeinschaft [SO1054/1, SP2202/SO1054/2, SPP 2202/LE721/17-1, SFB1064]
  2. National Institutes of Health [HG007743, HG003143, GM114190]
  3. National Institutes of Health (Center for 3D Structure and Physics of the Genome of NIH 4DN Consortium) [DK107980]

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Despite limited understanding of the spatial organization of the genome, this study demonstrates that highly expressed long genes form open-ended transcription loops with RNA polymerases moving along them. The extension and shape of these loops suggest intrinsic stiffness and could represent a general mechanism underlying eukaryotic transcription.
Despite the well-established role of nuclear organization in the regulation of gene expression, little is known about the reverse: how transcription shapes the spatial organization of the genome. Owing to the small sizes of most previously studied genes and the limited resolution of microscopy, the structure and spatial arrangement of a single transcribed gene are still poorly understood. Here we study several long highly expressed genes and demonstrate that they form open-ended transcription loops with polymerases moving along the loops and carrying nascent RNAs. Transcription loops can span across micrometres, resembling lampbrush loops and polytene puffs. The extension and shape of transcription loops suggest their intrinsic stiffness, which we attribute to decoration with multiple voluminous nascent ribonucleoproteins. Our data contradict the model of transcription factories and suggest that although microscopically resolvable transcription loops are specific for long highly expressed genes, the mechanisms underlying their formation could represent a general aspect of eukaryotic transcription.

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