Collapse transitions of a periodic hydrophilic hydrophobic chain

Orlandini, Enzo; Garel, Thomas

doi:10.1007/s100510050531

“…In other words, coarsening is always arrested. As suggested previously [20,23,25], specific binding creates loops and loop clustering is associated with entropic costs that scale super-linearly with loop number, and this limits cluster growth [23].…”

Section: Switching Proteins With Specific Binding Selfassemble Intmentioning

confidence: 64%

“…In the more complex case with specific DNA-binding interactions, clustering is associated with the formation of DNA loops. Looped structures incur an entropic cost which increases superlinearly with the number of loops, and can stop the growth of a cluster beyond a critical size [6,[23][24][25][26]. Such specific binding drives the formation of promoter-enhancer loops [2]; however there are several proteins which interact mainly non-specifically with large regions of the genome, such as histone H1 and other heterochromatin-associated proteins [2].…”

mentioning

confidence: 99%

Ephemeral Protein Binding to DNA Shapes Stable Nuclear Bodies and Chromatin Domains

Brackley

¹

,

Liebchen

²

,

Michieletto

³

et al. 2017

Biophysical Journal

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Fluorescence microscopy reveals that the contents of many (membrane-free) nuclear "bodies" exchange rapidly with the soluble pool whilst the underlying structure persists; such observations await a satisfactory biophysical explanation. To shed light on this, we perform large-scale Brownian dynamics simulations of a chromatin fiber interacting with an ensemble of (multivalent) DNA-binding proteins; these proteins switch between two states -active (binding) and inactive (non-binding). This system provides a model for any DNA-binding protein that can be modified post-translationally to change its affinity for DNA (e.g., like the phosphorylation of a transcription factor). Due to this out-of-equilibrium process, proteins spontaneously assemble into clusters of self-limiting size, as individual proteins in a cluster exchange with the soluble pool with kinetics like those seen in photo-bleaching experiments. This behavior contrasts sharply with that exhibited by "equilibrium", or non-switching, proteins that exist only in the binding state; when these bind to DNA non-specifically, they form clusters that grow indefinitely in size. Our results point to post-translational modification of chromatin-bridging proteins as a generic mechanism driving the self-assembly of highly dynamic, non-equilibrium, protein clusters with the properties of nuclear bodies. Such active modification also reshapes intra-chromatin contacts to give networks resembling those seen in topologically-associating domains, as switching markedly favors local (short-range) contacts over distant ones.In all living organisms, from bacteria to man, DNA and chromatin are invariably associated with binding proteins, which organize their structure [1][2][3]. Many of these architectural proteins are molecular bridges that can bind at two or more distinct DNA sites to form loops. For example, bacterial DNA is looped and compacted by the histone-like protein H-NS which has two distinct DNA-binding domains [4]. In eukaryotes, complexes of transcription factors and RNA polymerases stabilize enhancer-promoter loops [5,6,6, 7], while HP1 [9], histone H1 [10], and the polycomb-repressor complex PRC1/2 [5, 11] organize inactive chromatin. Proteins also bind to specific DNA sequences to form larger structures, like nucleoli and the histone-locus, Cajal, and promyeloleukemia bodies [13][14][15][16][17][18]. The selective binding of molecular bridges to active and inactive regions of chromatin has also been highlighted as one possible mechanism underlying the formation of topologically associated domains (TADs) -regions rich in local DNA interactions [6,6,19].From a biophysical perspective, a system made up of DNA and DNA-binding proteins exhibits many kinds of interesting and seemingly counter-intuitive behaviour, such as the clustering of proteins in the absence of any attractive interaction between them. This process is driven by the "bridging-induced attraction" [20]. In conjunction with the specific patterning of binding sites found on a whole human chromoso...

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“…(22) is a variant of the real Ginzburg-Landau equation, here describing, together with the coefficients Eqs. (23)(24)(25), the dynamics of chromatin and proteins close to the onset of instability. In this equation /(c t t u ) is the initial growth rate of protein clusters; x u /c 3 describes the amplitude of their saturation (related to their density) for a given X > √ A + √ D 2 and x u √ c x is a correlation length, describing a scale of spatial modulations of the saturation amplitude of DNA clusters.…”

Section: B Amplitude Equationsmentioning

confidence: 99%

Ephemeral protein binding to DNA shapes stable nuclear bodies and chromatin domains

Brackley

¹

,

Liebchen

²

,

Michieletto

³

et al. 2016

Preprint

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Fluorescence microscopy reveals that the contents of many (membrane-free) nuclear "bodies" exchange rapidly with the soluble pool whilst the underlying structure persists; such observations await a satisfactory biophysical explanation. To shed light on this, we perform large-scale Brownian dynamics simulations of a chromatin fiber interacting with an ensemble of (multivalent) DNAbinding proteins; these proteins switch between two states -active (binding) and inactive (nonbinding). This system provides a model for any DNA-binding protein that can be modified posttranslationally to change its affinity for DNA (e.g., like the phosphorylation of a transcription factor). Due to this out-of-equilibrium process, proteins spontaneously assemble into clusters of self-limiting size, as individual proteins in a cluster exchange with the soluble pool with kinetics like those seen in photo-bleaching experiments. This behavior contrasts sharply with that exhibited by "equilibrium", or non-switching, proteins that exist only in the binding state; when these bind to DNA non-specifically, they form clusters that grow indefinitely in size. Our results point to post-translational modification of chromatin-bridging proteins as a generic mechanism driving the self-assembly of highly dynamic, non-equilibrium, protein clusters with the properties of nuclear bodies. Such active modification also reshapes intra-chromatin contacts to give networks resembling those seen in topologically-associating domains, as switching markedly favors local (short-range) contacts over distant ones.

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“…where the first sum extends over nearest neighbors pairs of solvent cells in the two dimensional lattice, and the last sum extends over neighboring monomers of the SARW. A two dimensional SARW in isolation is known to undergo a collapse transition from an extended coil phase at high temperature to a globular collapsed state at low temperature at the critical temperature k B θ/ǫ ≈ 1.5 [17,18]. We then study the change in this collapse transition brought about by the solvent.…”

Section: Two Intermediate Scale (Or Coarse Grained) Models Of Hydrophmentioning

confidence: 99%

Collapse transition of a hydrophobic self-avoiding random walk in a coarse-grained model solvent

Gaudreault

¹

,

Viñals

²

2009

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In order to study solvation effects on protein folding, we analyze the collapse transition of a self-avoiding random walk composed of hydrophobic segments that is embedded in a lattice model of a solvent. As expected, hydrophobic interactions lead to an attractive potential of mean force among chain segments. As a consequence, the random walk in solvent undergoes a collapse transition at a higher temperature than in its absence. Chain collapse is accompanied by the formation of a region depleted of solvent around the chain. In our simulation, the depleted region at collapse is as large as our computational domain.

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Collapse transitions of a periodic hydrophilic hydrophobic chain

Cited by 7 publications

References 28 publications

Ephemeral Protein Binding to DNA Shapes Stable Nuclear Bodies and Chromatin Domains

Ephemeral Protein Binding to DNA Shapes Stable Nuclear Bodies and Chromatin Domains

Ephemeral protein binding to DNA shapes stable nuclear bodies and chromatin domains

Collapse transition of a hydrophobic self-avoiding random walk in a coarse-grained model solvent

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