Understanding Apparent DNA Flexibility Enhancement by HU and HMGB Architectural Proteins

Czapla, Luke; Peters, Justin P.; Rueter, Emily M.; Olson, Wilma K.; Maher, L. James

doi:10.1016/j.jmb.2011.03.050

Cited by 36 publications

(40 citation statements)

References 80 publications

(110 reference statements)

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“…The binding of a few nonspecific architectural proteins, such as the bacterial HU protein, can also account for the discrepancy in twist. The uptake of HU not only changes the torsional alignment of DNA against a loop-mediating protein but also enhances its propensity to adopt a closed structure (Czapla et al 2008; Czapla et al 2011; Czapla et al 2013). On the other hand, whether the Lac repressor adopts an opened state in the 452-bp protein-divided minicircle remains an open question.…”

Section: Discussionmentioning

confidence: 99%

“…We identify conditions under which the modeled DNA may assume different levels of supercoiling and find that the binding of repressor to evenly spaced operator sites brings the energies of different topoisomers within close range of one another. We ignore the large-scale opening of the Lac repressor detected in low-resolution structural studies (McKay et al 1982; Ruben and Roos 1997; Taraban et al 2008), the effects of non-specific architectural proteins on looping (Becker et al 2005; Czapla et al 2011), the fluctuations in DNA operator sequences on the repressor headpieces (Spronk et al 1999; Colasanti et al 2013), and the local, sequence-dependent structural and energetic properties of DNA (Olson et al 1998). The present article thus serves as a starting point for further investigation of the contributions of repressor deformability, architectural proteins, operator, minicircle chain length, and base-pair sequence to DNA topological organization.…”

Section: Introductionmentioning

confidence: 99%

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Insights into genome architecture deduced from the properties of short Lac repressor-mediated DNA loops

Perez

Olson

2016

Biophys Rev

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Genomic DNA is vastly longer than the space allotted to it in a cell. The molecule must fold with a level of organization that satisfies the imposed spatial constraints as well as allows for the processing of genetic information. Key players in this organization include the negative supercoiling of DNA, which facilitates the unwinding of the double-helical molecule, and the associations of DNA with proteins, which partition the DNA into isolated loops, or domains. In order to gain insight into the principles of genome organization and to visualize the folding of spatially constrained DNA, we have developed new computational methods to identify the preferred three-dimensional pathways of protein-mediated DNA loops and to characterize the topological properties of these structures. Here we focus on the levels of supercoiling and the spatial arrangements of DNA in model nucleoprotein systems with two topological domains. We construct these systems by anchoring DNA loops in opposing orientations on a common protein-DNA assembly, namely the Lac repressor protein with two bound DNA operators. The linked pieces of DNA form a covalently closed circle such that the protein attaches to two widely spaced sites along the DNA. We examine the effects of operator spacing, loop orientation, and long-range contacts on overall chain configuration and topology and discuss our findings in the context of classic experiments on the effects of supercoiling and operator spacing on Lac repressor-mediated looping and recent work on the role of proteins as barriers that divide genomes into independent topological domains.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insights into genome architecture deduced from the properties of short Lac repressor-mediated DNA loops

Perez

Olson

2016

Biophys Rev

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“…Olson and co-workers took the modeling of HU-DNA complexes beyond the traditional statistical mechanics approach by considering realistic three-dimensional (3D) structural and mechanical features. [19][20][21][22][23][24][25][26][27] The fact that their coarse-grained model was based on elastic forces made the realization of a great number of atoms possible. 28 Their numerical simulations revealed a number of interesting physical mechanisms, including HU-assisted loop formation 24,26 and DNA-directed sequence speci¯city of nonspeci¯c bending proteins.…”

Section: Introductionmentioning

confidence: 99%

A stochastic reaction-diffusion model for protein aggregation on DNA

Voulgarakis

2017

Int. J. Mod. Phys. C

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Vital functions of DNA, such as transcription and packaging, depend on the proper clustering of proteins on the double strand. The present study investigates how the interplay between DNA allostery and electrostatic interactions a®ects protein clustering. The statistical analysis of a simple but transparent computational model reveals two major consequences of this interplay. First, depending on the protein and salt concentration, protein¯laments exhibit a bimodal DNA sti®ening and softening behavior. Second, within a certain domain of the control parameters, electrostatic interactions can cause energetic frustration that forces proteins to assemble in rigid spiral con¯gurations. Such spiral¯laments might trigger both positive and negative supercoiling, which can ultimately promote gene compaction and regulate the promoter. It has been experimentally shown that bacterial histone-like proteins assemble in similar spiral patterns and/or exhibit the same bimodal behavior. The proposed model can, thus, provide computational insights into the physical mechanisms used by proteins to control the mechanical properties of the DNA.

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“…The random binding of the protein, at levels approximating those found in vivo, brings the predicted looping propensities in line with values deduced from geneexpression studies. The introduction of low levels of HU similarly enhances the formation of DNA minicircles (12), accounting for the very small rings detected in DNA ligation studies (13,14) and the ease of cyclization determined for longer chains at different concentrations of HU (15).…”

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confidence: 97%

DNA topology confers sequence specificity to nonspecific architectural proteins

Juan

Czapla

Grosner

et al. 2014

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

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Topological constraints placed on short fragments of DNA change the disorder found in chain molecules randomly decorated by nonspecific, architectural proteins into tightly organized 3D structures. The bacterial heat-unstable (HU) protein builds up, counter to expectations, in greater quantities and at particular sites along simulated DNA minicircles and loops. Moreover, the placement of HU along loops with the "wild-type" spacing found in the Escherichia coli lactose (lac) and galactose (gal ) operons precludes access to key recognition elements on DNA. The HU protein introduces a unique spatial pathway in the DNA upon closure. The many ways in which the protein induces nearly the same closed circular configuration point to the statistical advantage of its nonspecificity. The rotational settings imposed on DNA by the repressor proteins, by contrast, introduce sequential specificity in HU placement, with the nonspecific protein accumulating at particular loci on the constrained duplex. Thus, an architectural protein with no discernible DNA sequencerecognizing features becomes site-specific and potentially assumes a functional role upon loop formation. The locations of HU on the closed DNA reflect long-range mechanical correlations. The protein responds to DNA shape and deformability-the stiff, naturally straight double-helical structure-rather than to the unique features of the constituent base pairs. The structures of the simulated loops suggest that HU architecture, like nucleosomal architecture, which modulates the ability of regulatory proteins to recognize their binding sites in the context of chromatin, may influence repressoroperator interactions in the context of the bacterial nucleoid.NA behaves differently in a cellular milieu than in aqueous salt solution. Proteins attach to widely spaced sites along genomic sequences in vivo and force the intervening DNA into loops much shorter in length than those expected from the natural deformational properties of the double helix. For example, the control of gene expression in Escherichia coli entails the formation of short DNA loops, some ∼100 bp steps in length, that preclude access of RNA polymerase to the signals needed to transcribe the enzymes encoded within various operons (1, 2). DNA of the same length tends to be highly extended in vitro, with very low chances of closing spontaneously into a loop (3, 4).Aside from the proteins that hold specific sequences at the ends of short DNA loops in place, the cellular environment includes a number of other components that influence the properties of DNA loops. For example, the naturally abundant, nonspecific E. coli heat-unstable (HU) protein plays important roles both in cellular processing and in shaping the architecture of the bacterial nucleoid. The dimeric protein introduces large deformations in DNA-sharp bends, helical untwisting, and helical axis dislocation (5)-that are central to its activity. The binding of HU to an AT-rich sequence element stabilizes loops important for repression of the galactose (ga...

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Understanding Apparent DNA Flexibility Enhancement by HU and HMGB Architectural Proteins

Cited by 36 publications

References 80 publications

Insights into genome architecture deduced from the properties of short Lac repressor-mediated DNA loops

Insights into genome architecture deduced from the properties of short Lac repressor-mediated DNA loops

A stochastic reaction-diffusion model for protein aggregation on DNA

DNA topology confers sequence specificity to nonspecific architectural proteins

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