Supercoiling in DNA and chromatin

“The boundaries of TADS are enriched for CTCF binding sites.”

“The boundaries of TADS are enriched for CTCF binding sites.”

“The classic example is the ‘twin supercoiled domain’ model where elongating RNA polymerase, in unwinding the DNA, generates positive supercoiling ahead and, in rewinding the DNA, generates negative supercoiling in its wake [7,8] (Figure 1).”

“The genome is also separately organised into about 500 independent 10 kb supercoiling domains with demarcating barriers stochastically distributed and dynamically maintained [19,20].”

“Genes that are negatively supercoiled are generally more efficiently transcribed [9,10] but topoisomerase inhibition studies [11,12 ,13,14] indicate that the accumulation of excessive positive or negative supercoiling will repress transcription.”

“Although in vitro studies support this concept [5] its operation in vivo is elusive [6].”

“Condensins introduce global positive writhe into the DNA/chromatin in vitro [46] and as a result changes in supercoiling energy are thought to co-dependently drive mitotic chromosome architecture [47] and resolution in vivo.”

“To understand the nature of eukaryotic supercoiling domains, psoralen binding has been used in combination with microarrays to map the distribution of DNA supercoils across entire genomes [23] or to particular chromosomal regions [24 ,25 ].”

“[34 ], in a single-molecule approach, used an angular optical trap.”

“[33] used a tamoxifen-inducible Cre recombinase to excise a chromatin segment with its torsional stress trapped intact.”

“Genes that are negatively supercoiled are generally more efficiently transcribed [9,10] but topoisomerase inhibition studies [11,12 ,13,14] indicate that the accumulation of excessive positive or negative supercoiling will repress transcription.”

“The classic example is the ‘twin supercoiled domain’ model where elongating RNA polymerase, in unwinding the DNA, generates positive supercoiling ahead and, in rewinding the DNA, generates negative supercoiling in its wake [7,8] (Figure 1).”

“Genes that are negatively supercoiled are generally more efficiently transcribed [9,10] but topoisomerase inhibition studies [11,12 ,13,14] indicate that the accumulation of excessive positive or negative supercoiling will repress transcription.”

“On approaching mitosis the remaining catenations, or sister chromatid intertwinings are ‘identified’ by a process that involves an architectural change in chromatin structure, orchestrated by condensin-generated and mitotic spindle-dependant positive supercoiling [44].”

“The capacity of negative supercoiling to unwind DNA and facilitate processes such as transcription [29,30] and replication and its ability to induce alternative DNA structures such as cruciform [31], G-quadruplexes and Z-DNA [32] have been noted.”

“Condensins introduce global positive writhe into the DNA/chromatin in vitro [46] and as a result changes in supercoiling energy are thought to co-dependently drive mitotic chromosome architecture [47] and resolution in vivo.”

“Although we raised this issue, twenty-five years ago [38], the question essentially remains unanswered as the difficulty is multifaceted.”

“A build up of negative supercoiling propagates along the fibre, melting the FUSE element promoting the binding of the ssDNA binding proteins, FBP and FIR [33,48].”

“[3] with the Ter domain being subdivided into smaller, 35 kb domains via MatS/MatP interactions [18].”

“At the level of the ‘twin supercoil domain’ the scenario seems simplistic; positive supercoiling ahead of the polymerase will destabilize nucleosome structure and negative supercoiling behind will promote reassembly [36], actions that seem entirely consistent with the thermodynamic demands of transcription through a c…”

“The capacity of negative supercoiling to unwind DNA and facilitate processes such as transcription [29,30] and replication and its ability to induce alternative DNA structures such as cruciform [31], G-quadruplexes and Z-DNA [32] have been noted.”

“Therefore, there must be a regulated balance in the localised levels of supercoiling through the concerted actions of polymerases [15] and topoisomerases [16,17].”

“Chromatin–chromatin interactions may act as supercoil diffusion barriers but the inherent drag, and therefore reduced rotation, caused by higher levels of chromatin organisation could in itself be sufficient to form the basis of supercoiling domains [26,27].”

“[42] observed that inhibition of topoisomerase I and the build up of positive supercoiling caused replication delay in long but not short yeast chromosomes.”

“The capacity of negative supercoiling to unwind DNA and facilitate processes such as transcription [29,30] and replication and its ability to induce alternative DNA structures such as cruciform [31], G-quadruplexes and Z-DNA [32] have been noted.”

“Therefore, there must be a regulated balance in the localised levels of supercoiling through the concerted actions of polymerases [15] and topoisomerases [16,17].”

“Genes that are negatively supercoiled are generally more efficiently transcribed [9,10] but topoisomerase inhibition studies [11,12 ,13,14] indicate that the accumulation of excessive positive or negative supercoiling will repress transcription.”

“[3] with the Ter domain being subdivided into smaller, 35 kb domains via MatS/MatP interactions [18].”

“Concomitantly, chromosome compaction starts during S-phase when condensin II is recruited to replicated regions [45].”

“If these are not efficiently removed the residual energy may influence DNA or chromatin structure locally [28], or, if the energy can be propagated along the fibre, at more distant sites.”

“Genes that are negatively supercoiled are generally more efficiently transcribed [9,10] but topoisomerase inhibition studies [11,12 ,13,14] indicate that the accumulation of excessive positive or negative supercoiling will repress transcription.”

“To understand the nature of eukaryotic supercoiling domains, psoralen binding has been used in combination with microarrays to map the distribution of DNA supercoils across entire genomes [23] or to particular chromosomal regions [24 ,25 ].”

“The genome is also separately organised into about 500 independent 10 kb supercoiling domains with demarcating barriers stochastically distributed and dynamically maintained [19,20].”

“Genes that are negatively supercoiled are generally more efficiently transcribed [9,10] but topoisomerase inhibition studies [11,12 ,13,14] indicate that the accumulation of excessive positive or negative supercoiling will repress transcription.”

“The capacity of negative supercoiling to unwind DNA and facilitate processes such as transcription [29,30] and replication and its ability to induce alternative DNA structures such as cruciform [31], G-quadruplexes and Z-DNA [32] have been noted.”

“Nucleosomes containing yeast histones are more sensitive to thermally induced torsional stress [39] than nucleosomes containing higher eukaryotic core histones suggesting, perhaps, a greater propensity for yeast chromatin to absorb rather than transmit negative supercoiling.”

“(b) Negative supercoiling promotes ssDNA patch formation allowing the mutagenic activity of activation-induced cytidine deaminase (AID) [35 ].”

“Although in vitro studies support this concept [5] its operation in vivo is elusive [6].”

“Although there is no direct evidence for the transmission of torsion through chromatin the phenomenon is used to explain the apparent dissipation of positive supercoiling near theendsofyeastchromosomes[41].”

“Therefore, there must be a regulated balance in the localised levels of supercoiling through the concerted actions of polymerases [15] and topoisomerases [16,17].”

“However, the many models that purport to explain the mechanics of how polymerase does in fact transcribe through a nucleosome reflects our ignorance of the details [37].”

“Chromatin–chromatin interactions may act as supercoil diffusion barriers but the inherent drag, and therefore reduced rotation, caused by higher levels of chromatin organisation could in itself be sufficient to form the basis of supercoiling domains [26,27].”

“However, when converging forks approach, relaxation of positive supercoiling is restricted and the build up of torsional stress causes swivelling of the replication complex required to complete replication [43 ].”

“If loops are preformed into left-handed (or right-handed) inter-wound supercoils (53), pyramids are more sharply defined (Figure 3E; these results are also consistent with those obtained in (21,33)).”

“Together, these results suggested that the difference in cleavage activity between PCR amplicons and endogenous intracellular loci might be related to various effects of the intracellular condition, such as degradation issues by DNA exonuclease (29), structural hindrances by binding of histones or other proteins (30),…”