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Review
. 2014 May-Jun;5(3):195-202.
doi: 10.4161/nucl.28909. Epub 2014 Apr 22.

DNA topology and transcription

Fedor Kouzine  1 , David Levens  1 , Laura Baranello  1
Affiliations
Review

DNA topology and transcription

Fedor Kouzine et al. Nucleus. 2014 May-Jun.

Abstract

Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions.

Keywords: DNA topoisomerases; DNA topological domain; DNA topology; torsional stress; transcription.

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Figures

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Figure 1. Topological domains of DNA during cellular processes. (A) By definition a topological domain requires topologically constrained DNA ends. Within a domain, genetic transactions can distort the structure of the double helix and generate supercoilings, eventually removed through the relaxation activity of DNA topoisomerases or the transitions of regular B-DNA into non-B DNA conformations (Z-DNA is shown as example). Topological domains can be identified at many hierarchical levels: (B) in the linker region between two adjacent nucleosome; (C) during transcriptional elongation where the RNA polymerase constitutes a moving node between fixed ends; and (D) during enhancer-promoter interaction.
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Figure 2. Transcription is associated with dynamic perturbation of DNA. (A) Negative DNA supercoiling occurs at upstream promoter regions of every transcribed gene. (B) Nucleosome mobilization potential is differentially affected upstream and downstream of transcribing RNA polymerase. (C) Non-B DNA formed as result of ongoing transcription has the capacity to regulate the promoter output in real-time. (D) The activity of divergent closely juxtaposed promoters may be mechanically coupled through dynamic supercoiling. (E) Enhancer transcription could be required to generate torsional stress which results in reorganization of local chromatin structure and favors enhancer-promoter communication.
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Comment on

  • Kouzine F1, Gupta A, Baranello L, Wojtowicz D, Ben-Aissa K, Liu J, Przytycka TM, Levens D. Transcription-dependent dynamic supercoiling is a short-range genomic force. Nat Struct Mol Biol. 2013;20:396–403. doi: 10.1038/nsmb.2517.

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