ISWI Remodelers Slide Nucleosomes with Coordinated Multi-Base-Pair Entry Steps and Single-Base-Pair Exit Steps

Deindl, Sebastian; Hwang, William L.; Hota, Swetansu K.; Blosser, Timothy R.; Prasad, Punit; Bartholomew, Blaine; Zhuang, Xiaowei

doi:10.1016/j.cell.2012.12.040

Cited by 167 publications

(220 citation statements)

References 66 publications

Supporting

Mentioning

197

Contrasting

Order By: Relevance

“…These ATP-driven proteins have the capability to disrupt nucleosome-DNA contacts, move nucleosomes along DNA, and remove or exchange nucleosomes (41)(42)(43). The remodeling complexes translocate nucleosomes in small well-defined steps (44,45). Thus, nucleosome positions are dynamically controlled on the level of individual nucleosomes by the cell.…”

Section: Introductionmentioning

confidence: 98%

Changing Chromatin Fiber Conformation by Nucleosome Repositioning

Müller

Kepper

Schöpflin

et al. 2014

Biophysical Journal

View full text Add to dashboard Cite

Chromatin conformation is dynamic and heterogeneous with respect to nucleosome positions, which can be changed by chromatin remodeling complexes in the cell. These molecular machines hydrolyze ATP to translocate or evict nucleosomes, and establish loci with regularly and more irregularly spaced nucleosomes as well as nucleosome-depleted regions. The impact of nucleosome repositioning on the three-dimensional chromatin structure is only poorly understood. Here, we address this issue by using a coarse-grained computer model of arrays of 101 nucleosomes considering several chromatin fiber models with and without linker histones, respectively. We investigated the folding of the chain in dependence of the position of the central nucleosome by changing the length of the adjacent linker DNA in basepair steps. We found in our simulations that these translocations had a strong effect on the shape and properties of chromatin fibers: i), Fiber curvature and flexibility at the center were largely increased and long-range contacts between distant nucleosomes on the chain were promoted. ii), The highest destabilization of the fiber conformation occurred for a nucleosome shifted by two basepairs from regular spacing, whereas effects of linker DNA changes of ?10 bp in phase with the helical twist of DNA were minimal. iii), A fiber conformation can stabilize a regular spacing of nucleosomes inasmuch as favorable stacking interactions between nucleosomes are facilitated. This can oppose nucleosome translocations and increase the energetic costs for chromatin remodeling. Our computational modeling framework makes it possible to describe the conformational heterogeneity of chromatin in terms of nucleosome positions, and thus advances theoretical models toward a better understanding of how genome compaction and access are regulated within the cell.

show abstract

Section: Introductionmentioning

confidence: 98%

Changing Chromatin Fiber Conformation by Nucleosome Repositioning

Müller

Kepper

Schöpflin

et al. 2014

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…Several single-molecule measurements suggest a repositioning mechanism that cannot be classified into any of these models (36,37). There is considerable evidence in support of each model, and it is likely that these repositioning mechanisms are not mutually exclusive but arise depending on other factors, including the DNA sequence (38).…”

Section: Significancementioning

confidence: 99%

“…Some of the effects of DNA sequence on nucleosome mobility have been explored (21,36,39). However, the vast majority of studies on nucleosome repositioning (22,37,(40)(41)(42)(43)(44) have only considered the 601 positioning sequence (9), which exhibits a particularly strong affinity for histones. Such studies have led to valuable insights, but it remains unclear if or to what extent observations pertaining to the 601 sequence can be generalized to other, naturally occurring, nonsynthetic, DNA sequences.…”

Section: Significancementioning

confidence: 99%

In silico evidence for sequence-dependent nucleosome sliding

Lequieu

Schwartz

Pablo

2017

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

107

View full text Add to dashboard Cite

Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA sequence and the dynamic action of other proteins within the nucleus. These processes are central to cellular function, and the molecular details of the interplay between DNA sequence and nucleosome dynamics remain poorly understood. In this work, we investigate this interplay in detail by relying on a molecular model, which permits development of a comprehensive picture of the underlying free energy surfaces and the corresponding dynamics of nucleosome repositioning. The mechanism of nucleosome repositioning is shown to be strongly linked to DNA sequence and directly related to the binding energy of a given DNA sequence to the histone core. It is also demonstrated that chromatin remodelers can override DNA-sequence preferences by exerting torque, and the histone H4 tail is then identified as a key component by which DNA-sequence, histone modifications, and chromatin remodelers could in fact be coupled.nucleosome repositioning | chromatin dynamics | molecular simulation | advanced sampling techniques T he basic building block of eukaryotic chromatin is the nucleosome, a DNA-protein complex containing 147 bp of DNA wrapped around a disk-like protein complex known as the histone octamer (1). Since nucleosomal DNA is inaccessible to other DNA-binding proteins, such as transcription factors and polymerases (2-4), the locations of nucleosomes represent an important mechanism by which cellular processes are controlled. Notably, nucleosome positions are dynamic, with changes in transcription levels, cellular state, and environmental factors resulting in different packagings of chromatin (5, 6). Proper packaging of genomic DNA is critical to cellular function, and a wide range of human diseases have been associated with defects in chromatin structure (7,8). Understanding the molecular factors that control the locations of nucleosomes, and how they are dynamically modulated, therefore represents a central goal of molecular biology and biophysics.It is now appreciated that the DNA sequence itself represents a key factor that governs the locations of nucleosomes. Different DNA sequences exhibit different affinities for the histone proteins, and as such, they form nucleosomes with probabilities that can differ by several orders of magnitude (9, 10). The dependence of nucleosome locations on DNA sequence originates from subtle differences in the intrinsic shape and flexibility of a specific DNA sequence, which lead to favorable electrostatic interactions between the DNA backbone and residues on the histone surface (11). In fact, this pronounced dependence on DNA sequence has led several authors to propose that a genetic code exists (12, 13) where the positions of 50% of nucleosomes in vivo are dictated by DNA sequence alone. Such a view, however, is not without controversy (14, 15),...

show abstract

“…This is what would be expected from a translocase that tracks the helical groove of DNA while clinging to an initial anchor point, although the enzyme seems to lose its grip occasionally during translocation and hence does not create a predictable amount of unwinding per base pairs traversed. Nonetheless chromatin remodeling proteins such as those in the Snf2 family of proteins can act as specialized DNA translocases that catalyze DNA unwinding (Havas et al 2000), which is associated with catalyzing the movement of DNA across the surface of the nucleosome (Deindl et al 2013).…”

Section: Dna Bending Stiffness Modulates the Activity Of Topoisomerasmentioning

confidence: 99%

Supercoiling biases the formation of loops involved in gene regulation

Finzi

Dunlap

2016

Biophys Rev

View full text Add to dashboard Cite

The function of DNA as a repository of genetic information is well-known. The post-genomic effort is to understand how this information-containing filament is chaperoned to manage its compaction and topological states. Indeed, the activities of enzymes that transcribe, replicate, or repair DNA are regulated to a large degree by access. Proteins that act at a distance along the filament by binding at one site and contacting another site, perhaps as part of a bigger complex, create loops that constitute topological domains and influence regulation. DNA loops and plectonemes are not necessarily spontaneous, especially large loops under tension for which high energy is required to bring their ends together, or small loops that require accessory proteins to facilitate DNA bending. However, the torsion in stiff filaments such as DNA dramatically modulates the topology, driving it from extended and genetically accessible to more looped and compact, genetically secured forms. Furthermore, there are accessory factors that bias the response of the DNA filament to supercoiling. For example, small molecules like polyamines, which neutralize the negative charge repulsions along the phosphate backbone, enhance flexibility and promote writhe over twist in response to torsion. Such increased flexibility likely pushes the topological equilibrium from twist toward writhe at tensions thought to exist in vivo. A predictable corollary is that stiffening DNA antagonizes looping and bending. Certain sequences are known to be more or less flexible or to exhibit curvature, and this may affect interactions with binding proteins. In vivo all of these factors operate simultaneously on DNA that is generally negatively supercoiled to some degree. Therefore, in order to better understand gene regulation that involves protein-mediated DNA loops, it is critical to understand the thermodynamics and kinetics of looping in DNA that is under tension, negatively supercoiled, and perhaps exposed to molecules that alter elasticity. Recent experiments quantitatively reveal how much negatively supercoiling DNA lowers the free energy of looping, possibly biasing the operation of genetic switches.

show abstract

ISWI Remodelers Slide Nucleosomes with Coordinated Multi-Base-Pair Entry Steps and Single-Base-Pair Exit Steps

Cited by 167 publications

References 66 publications

Changing Chromatin Fiber Conformation by Nucleosome Repositioning

Changing Chromatin Fiber Conformation by Nucleosome Repositioning

In silico evidence for sequence-dependent nucleosome sliding

Supercoiling biases the formation of loops involved in gene regulation

Contact Info

Product

Resources

About