The functional response of upstream DNA to dynamic supercoiling in vivo

Kouzine, Fedor; Sanford, Suzanne; Elisha-Feil, Zichrini; Levens, David

doi:10.1038/nsmb.1372

Cited by 266 publications

(353 citation statements)

References 57 publications

Supporting

Mentioning

341

Contrasting

Order By: Relevance

“…In regions of very active transcription, topoisomerase‐mediated resolution of the negative supercoiling generated in the wake of RNAPII does not appear to be able to keep pace resulting in overall negative supercoiling upstream of RNAPII (Kouzine et al , 2008). Negative supercoiling creates localised denaturation bubbles (Jeon et al , 2010), which have been shown to provide an ideal substrate for AID on both strands of a plasmid, even in the absence of transcription (Shen & Storb, 2004; Shen et al , 2005).…”

Section: Discussionmentioning

confidence: 99%

Histone H3.3 promotes IgV gene diversification by enhancing formation of AID ‐accessible single‐stranded DNA

et al. 2016

View full text Add to dashboard Cite

Immunoglobulin diversification is driven by activation‐induced deaminase (AID), which converts cytidine to uracil within the Ig variable (IgV) regions. Central to the recruitment of AID to the IgV genes are factors that regulate the generation of single‐stranded DNA (ssDNA), the enzymatic substrate of AID. Here, we report that chicken DT40 cells lacking variant histone H3.3 exhibit reduced IgV sequence diversification. We show that this results from impairment of the ability of AID to access the IgV genes due to reduced formation of ssDNA during IgV transcription. Loss of H3.3 also diminishes IgV R‐loop formation. However, reducing IgV R‐loops by RNase HI overexpression in wild‐type cells does not affect IgV diversification, showing that these structures are not necessary intermediates for AID access. Importantly, the reduction in the formation of AID‐accessible ssDNA in cells lacking H3.3 is independent of any effect on the level of transcription or the kinetics of RNAPII elongation, suggesting the presence of H3.3 in the nucleosomes of the IgV genes increases the chances of the IgV DNA becoming single‐stranded, thereby creating an effective AID substrate.

show abstract

Section: Discussionmentioning

confidence: 99%

Histone H3.3 promotes IgV gene diversification by enhancing formation of AID ‐accessible single‐stranded DNA

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The relationship between DNA topology and gene expression is not unidirectional: transcription itself creates topological change in the DNA template, so environmental factors that influence transcription initiation, elongation or termination all have the potential to modulate the superhelicity of the DNA in the genome (Bohrer and Roberts 2016;Kouzine et al 2008;Kotlajich et al 2015;Ma and Wang 2014a).…”

Section: An Environmentally Responsive Global Regulatory Systemmentioning

confidence: 99%

DNA supercoiling is a fundamental regulatory principle in the control of bacterial gene expression

Dorman

2016

Biophys Rev

104

View full text Add to dashboard Cite

Although it has become routine to consider DNA in terms of its role as a carrier of genetic information, it is also an important contributor to the control of gene expression. This regulatory principle arises from its structural properties. DNA is maintained in an underwound state in most bacterial cells and this has important implications both for DNA storage in the nucleoid and for the expression of genetic information. Underwinding of the DNA through reduction in its linking number potentially imparts energy to the duplex that is available to drive DNA transactions, such as transcription, replication and recombination. The topological state of DNA also influences its affinity for some DNA binding proteins, especially in DNA sequences that have a high A + T base content. The underwinding of DNA by the ATP-dependent topoisomerase DNA gyrase creates a continuum between metabolic flux, DNA topology and gene expression that underpins the global response of the genome to changes in the intracellular and external environments. These connections describe a fundamental and generalised mechanism affecting global gene expression that underlies the specific control of transcription operating through conventional transcription factors. This mechanism also provides a basal level of control for genes acquired by horizontal DNA transfer, assisting microbial evolution, including the evolution of pathogenic bacteria.

show abstract

“…Any effects would depend on how far such gradients extend. Current estimates suggest that, depending on the strength of the signal, gradients may extend for up to a few kilobases (Krasilnikov et al 1999;Moulin et al 2005;Kouzine et al 2008), and therefore their influence will be local rather than global (Sobetzko 2016;Meyer and Beslon 2014). Since transcription is a dominant source of the local generation of superhelicity, the relative orientation of neighboring genes determines how transcription of one may affect the activity of its neighbor by supercoilingmediated coupling.…”

Section: Gradients Of Superhelicity and Protein Bindingmentioning

confidence: 99%

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

Muskhelishvili

Travers

2016

Biophys Rev

View full text Add to dashboard Cite

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 ...

show abstract

The functional response of upstream DNA to dynamic supercoiling in vivo

Cited by 266 publications

References 57 publications

Histone H3.3 promotes IgV gene diversification by enhancing formation of AID ‐accessible single‐stranded DNA

Histone H3.3 promotes IgV gene diversification by enhancing formation of AID ‐accessible single‐stranded DNA

DNA supercoiling is a fundamental regulatory principle in the control of bacterial gene expression

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

Contact Info

Product

Resources

About