Spatial organization of transcribed eukaryotic genes

Susanne Leidescher, Johannes Ribisel, Simon Ullrich, Yana Feodorova, Erica Hildebrand, Alexandra Galitsyna, Sebastian Bultmann, Stephanie Link, Katharina Thanisch, Christopher Mulholland, Job Dekker, Heinrich Leonhardt, Leonid Mirny, Irina Solovei

bioRxiv (April, 2021) doi:10.1101/2020.05.20.106591v2

Abstract

Despite the well-established role of nuclear organization in gene expression regulation, little is known about the reverse: how transcription shapes the spatial organization of the genome. Owing to 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 make use of several long highly expressed genes and demonstrate that they form transcription loops with polymerases moving along the loops and carrying nascent RNAs. Transcription loops can span across microns resembling lampbrush loops and polytene puffs. Extension and shape of transcription loops suggest their intrinsic stiffness, which we attribute to decoration with multiple voluminous nascent RNPs. Our data contradict the model of transcription factories and indicate that although microscopically resolvable transcription loops are specific for long highly expressed genes, the mechanisms underlying their formation can represent a general aspect of eukaryotic transcription.

HiGlass Displays

Hi-C data for 4 tissues (4 panels in each row: Thyroid, Myotubes, Myoblasts, Bladder) positioned to show local chromosome organization around studied long and highly-transcribed genes. For each gene we highlight tissue(s) where this gene is highly expressed by the red bar above the map.

Thyroglobulin gene (Tg) coding for the extracellular protein thyroglobulin secreted by thyrocytes. Tg is highly expressed in thyroid gland, but not in other tissues.
Titin (Ttn) is a structural proteins of the contractile machineries of skeletal muscle. Ttn is highly expressed in myotubes.
Nebulin (Neb) is another structural protein of the contractile machineries. Neb is highly expressed in myotubes.
Myh11
Myosin Heavy Chain (Myh11) is tissue-specific for smooth muscle tissue. Myh11 is highly expressed in bladder myocytes.
Cald1
Caldesmon 1 (Cald1) is another gene of smooth muscle. Cald1 is highly expressed in both myoblasts and bladder tissue.