The loop extrusion theory predicts that cohesin acts as a molecular motor that extrudes chromatin fibers to produce loops. Hi-C experiments have detected relatively high contact frequencies between superenhancers. These probably result from the fact that superenhancers are localized at condensates of transcriptional activators and coactivators. The contact frequency between superenhancers is enhanced by auxin treatment that removes cohesin from chromatin. Motivated by these experimental results, we here treat chromatin at the surface of a condensate as a loop extruding polymer brush. Our theory predicts that the lateral pressure generated by the brush decreases with decreasing the loading rate of cohesin. This is because loop extrusion actively transfers chain segments at the vicinity of the interface. Our theory thus predicts that the increase of contact frequency by auxin treatment results from the fact that suppressing the loop extrusion process induces the dissolution of molecular components to the nucleoplasm, decreasing the average distance between superenhancers.
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http://dx.doi.org/10.1039/c9sm01454c | DOI Listing |
Sci Adv
January 2025
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. It is well established that cohesin is essential for TAD and loop connectivity features in Hi-C, but the corresponding change in physical structure has not been studied using electron microscopy. Pairing chromatin scanning transmission electron tomography with multiomic analysis and single-molecule localization microscopy, we study the role of cohesin in regulating the conformationally defined chromatin nanoscopic packing domains.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia.
Dictyostelium discoideum is a unicellular slime mold, developing into a multicellular fruiting body upon starvation. Development is accompanied by large-scale shifts in gene expression program, but underlying features of chromatin spatial organization remain unknown. Here, we report that the Dictyostelium 3D genome is organized into positionally conserved, largely consecutive, non-hierarchical and weakly insulated loops at the onset of multicellular development.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biology, Indiana University, 1001 E 3rd Street, Bloomington, IN 47405, USA.
Genome organization is important for DNA replication, gene expression, and chromosome segregation. In bacteria, two large families of proteins, nucleoid-associated proteins (NAPs) and SMC complexes, play important roles in organizing the genome. NAPs are highly abundant DNA-binding proteins that can bend, wrap, bridge, and compact DNA, while SMC complexes load onto the chromosome, translocate on the DNA, and extrude DNA loops.
View Article and Find Full Text PDFCurr Opin Genet Dev
January 2025
School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; New Cornerstone Science Laboratory, Westlake University, Hangzhou, Zhejiang, China. Electronic address:
Chromosomes in eukaryotic cells undergo compaction at multiple levels and are folded into hierarchical structures to fit into the nucleus with limited dimensions. Three-dimensional genome organization needs to be coordinated with chromosome-templated processes, including DNA replication and gene transcription. As an ATPase molecular machine, the cohesin complex is a major driver of genome folding, which regulates transcription by modulating promoter-enhancer contacts.
View Article and Find Full Text PDFCell
January 2025
Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands. Electronic address:
Structural maintenance of chromosomes (SMC) complexes organize the genome via DNA loop extrusion. Although some SMCs were reported to do so symmetrically, reeling DNA from both sides into the extruded DNA loop simultaneously, others perform loop extrusion asymmetrically toward one direction only. The mechanism underlying this variability remains unclear.
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