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. Author manuscript; available in PMC: 2022 Jul 1.
Published in final edited form as: Nat Rev Mol Cell Biol. 2016 Sep 21;17(11):703–721. doi: 10.1038/nrm.2016.111

Figure 2 |. Topoisomerases and transcription.

Figure 2 |

Transcription incurs topological constraints that result from the progression of RNA polymerase II (Pol II). Positive supercoiling (Sc+) of the DNA template takes place ahead of the transcription bubble, which in turn obstructs further Pol II movement, and negative supercoiling (Sc−), which promotes the formation of RNA–DNA hybrids (R loops), accumulates behind it. TOP2 and especially TOP1 enzymes function ahead of Pol II to remove positive supercoils, whereas relaxation of negative supercoils behind the transcription apparatus relies on TOP1 and TOP3β. In addition, TOP1 regulates the activity of the transcription factor TATA-box-binding protein (TBP) at promoter TATA boxes independently of its catalytic activity. The formation of TOP2β-mediated transient DNA double-stranded breaks at promoter regions in certain genes is crucial for transcription activation. TOP1 is also recruited to certain enhancer regions to promote (ligand-dependent) enhancer activation by generating transient DNA single-stranded breaks. Topological barriers are genomic regions where the DNA is not free to rotate around its axis and require TOP1 and TOP2 to relax supercoils (Sc). TF, transcription factor.