Transcription-dependent dynamic supercoiling is a short-range genomic force

Kouzine, Fedor; Gupta, Ashutosh; Baranello, Laura; Wójtowicz, Damian; Ben-Aissa, Khadija; Liu, Juhong; Przytycka, Teresa M.; Levens, David

doi:10.1038/nsmb.2517

Cited by 287 publications

(372 citation statements)

References 59 publications

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“…From a topological point of view, when two DNA segments interact with each other, they generate a closed domain within which a process that unwinds or distorts the double helix, e.g., transcription via dynamic supercoiling, can distort the geometry of DNA and change its properties to favor formation of looped, wrapped, or melted structures that are highenergy intermediates in DNA transactions. Depending on the size and shape of the confining topological domain, the dynamic torsional stress introduced by tracking proteins such as RNA polymerase (15) can be transmitted along the helix (16), influencing the expression of neighboring loci (17). In this…”

Section: Dna Interactions Within Chromosomal Territoriesmentioning

confidence: 99%

CTCF and cohesin cooperate to organize the 3D structure of the mammalian genome

Baranello

Kouzine

Levens

2014

Proc. Natl. Acad. Sci. U.S.A.

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Section: Dna Interactions Within Chromosomal Territoriesmentioning

confidence: 99%

CTCF and cohesin cooperate to organize the 3D structure of the mammalian genome

Baranello

Kouzine

Levens

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, recent genome-wide experiments suggest that cells have elaborate mechanisms to coordinate the rates of transcription and the DNA relaxing activity of topoisomerases to adjust supercoiling in the promoter regions of differentially expressed genes. 39,40 The mechanics of promoter melting by TFIIH subunits has been a long standing question. Because the ATPase has helicase activity in vitro, it was thought that TFIIH directly separates the two strands of the DNA double helix to form the transcriptional bubble.…”

Section: Dna Topology and Initiation Of Transcriptionmentioning

confidence: 99%

DNA topology and transcription

Kouzine¹,

Levens²,

Baranello³

2014

Nucleus

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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.

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“…These include cruciforms, slipped loops, Z-DNA, H-DNA and two-stranded structures containing the Gquadruplex motif (Lilley 1980;Singleton et al 1982;Voloshin et al 1992;Mace et al 1983;Minyat et al 1995;Sun and Hurley 2009;Kouzine et al 2013;Selvam et al 2014). While these serve as binding sites for particular proteins, they may also function as topological switches to absorb or release superhelicity in topologically sensitive regions such as promoters (Travers and Muskhelishvili 2015).…”

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confidence: 99%

The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

Muskhelishvili

Travers

2016

Biophys Rev

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We argue that dynamic changes in DNA supercoiling in vivo determine both how DNA is packaged and how it is accessed for transcription and for other manipulations such as recombination. In both bacteria and eukaryotes, the principal generators of DNA superhelicity are DNA translocases, supplemented in bacteria by DNA gyrase. By generating gradients of superhelicity upstream and downstream of their site of activity, translocases enable the differential binding of proteins which preferentially interact with respectively more untwisted or more writhed DNA. Such preferences enable, in principle, the sequential binding of different classes of protein and so constitute an essential driver of chromatin organization.Keywords DNA supercoiling . DNA translocases . Chromatin organization . Superhelicity gradients . DNA untwisting . DNAwrithing Dynamic changes of DNA supercoiling act as a driving force behind the alterations of genetic activity and DNA compaction both in eukaryotes and prokaryotes. Both these processes involve formation of spatially organized nucleoprotein structures by DNA architectural proteins. Whereas in eukaryotes the paradigmal example is the histone octamer, in prokaryotes a similar function is attributed to a small class of highly abundant nucleoid-associated proteins. We argue that, depending on the primary sequence organization, the changes of superhelicity elicit various alterations of local DNA geometry, while these, in turn, facilitate the assembly of distinct nucleoprotein structures pertinent to genetic function. Genome-wide conversion of the superhelical energy into various three-dimensional DNA structures thus acts as an analogue code coordinating the energy supply with the genetic expression of the chromosome.Recent studies make it increasingly clear that the DNA double helix carries at least two types of encoded information and that these include the well-known genetic code and the structural information determining the form and physical properties of the double helix itself. Since both these information types are inscribed in the same DNA sequence, and yet one is discrete whereas the other is continuous, they have been respectively dubbed the digital and analog DNA codes (Marr et al. 2008;Travers et al. 2012;Muskhelishvili and Travers 2013). The potential of the DNA to adopt distinct configurations is strongly modulated by DNA supercoiling, which is increasingly recognized as one of the major forces coordinating the cellular DNA transactions in both prokaryotes (including Archaea) and eukaryotes.DNA supercoiling can be generated by the simple application of torque to the double helix (Strick et al. 1998) but, importantly, because the DNA molecule itself possesses chirality-it is, after all, a right-handed double helix-the local structures stabilized by changes in superhelical density depend on both the sign and strength of the applied torque. For example, both positive and negative torque (respectively overand underwinding of the double helix) can change the intrinsic coiling of ...

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Transcription-dependent dynamic supercoiling is a short-range genomic force

Cited by 287 publications

References 59 publications

CTCF and cohesin cooperate to organize the 3D structure of the mammalian genome

CTCF and cohesin cooperate to organize the 3D structure of the mammalian genome

DNA topology and transcription

The regulatory role of DNA supercoiling in nucleoprotein complex assembly and genetic activity

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