Protein-mediated loops in supercoiled DNA create large topological domains

• Type of Material: Article
• Authors: Yan Yan, Emory University; Yue Ding, Emory University; Fenfei Leng, Florida International University; David Dunlap, Emory University; Laura Finzi, Emory University
• Language: English
• Date: 2018-05-18
• Publisher: Oxford University Press (OUP): Policy C - Option B
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/nar/gky153
• Title of Journal or Parent Work: Nucleic Acids Research
• ISSN: 0305-1048
• Volume: 46
• Issue: 9
• Start Page: 4417
• End Page: 4424
• Grant/Funding Information: Funding for open access charge: National Institutes of Health [R01GM084070].; National Institutes of Health [R01GM084070 to L.F., 1R15GM109254-01A1 to F.L.].
• Keywords: CHROMATIN DOMAINS; Life Sciences & Biomedicine; TETHERED-PARTICLE MOTION; SINGLE-MOLECULE; KINETICS; ESCHERICHIA-COLI; RNA; Science & Technology; LAC REPRESSOR; SIGNAL; TRANSCRIPTION; CHROMOSOME ORGANIZATION; Biochemistry & Molecular Biology
• Research Categories: Physics, General; Chemistry, Biochemistry

Abstract

Supercoiling can alter the form and base pairing of the double helix and directly impact protein binding. More indirectly, changes in protein binding and the stress of supercoiling also influence the thermodynamic stability of regulatory, protein-mediated loops and shift the equilibria of fundamental DNA/chromatin transactions. For example, supercoiling affects the hierarchical organization and function of chromatin in topologically associating domains (TADs) in both eukaryotes and bacteria. On the other hand, a protein-mediated loop in DNA can constrain supercoiling within a plectonemic structure. To characterize the extent of constrained supercoiling, 400 bp, lac repressor-secured loops were formed in extensively over- or under-wound DNA under gentle tension in a magnetic tweezer. The protein-mediated loops constrained variable amounts of supercoiling that often exceeded the maximum writhe expected for a 400 bp plectoneme. Loops with such high levels of supercoiling appear to be entangled with flanking domains. Thus, loop-mediating proteins operating on supercoiled substrates can establish topological domains that may coordinate gene regulation and other DNA transactions across spans in the genome that are larger than the separation between the binding sites.