Spatial organization of transcribed eukaryotic genes (ChIP-seq)

The nuclear organization of the genome is accepted as an important feature of gene expression regulation. However, it has remained unknown what the spatial organization of a single transcribed gene is. Here, we made use of several long highly expressed mammalian genes to describe their structure and spatial arrangement during transcription. We demonstrate that an expressed gene forms a transcription loop with RNA polymerases moving along the loop and carrying nascent RNAs that undergo co-transcriptional splicing. Transcription loops dynamically modify their harboring loci and extend into the nuclear interior due to their intrinsic stiffness. We hypothesize that the stiffness of the transcription loop arises due to a dense decoration of gene-axis with multiple voluminous nascent ribonucleoprotein particles, thus creating a stiff polymer bottlebrush. and provide supporting evidence to this hypothesis. Our work suggests that transcription loop formation is a universal principle of eukaryotic gene expression.