Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualizedinvivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA.We also identify architectural ?stripes,? where a loop anchor interacts with entire domains at highfrequency. Stripes often tether super-enhancers to cognate promoters, and in B cells, they facilitateIghtranscription and recombination. Stripe anchors represent major hotspots for topoisomerase-mediated lesions, which promote chromosomal translocations and cancer. In plasmacytomas, stripes can deregulateIgh-translocated oncogenes. We propose that higher organisms have coopted cohesin extrusion to enhance transcription and recombination, with implications for tumor development. SOURCE: Seolkyoung JungCasellas lab NIH

Pluto Bioinformatics

GSE98119: The energetics and physiological impact of cohesin extrusion