Kinetic Control of Nucleosome Displacement by ISWI/ACF Chromatin Remodelers

Florescu, Ana-Maria; Schiessel, Helmut; Blossey, Ralf

doi:10.1103/physrevlett.109.118103

Cited by 18 publications

(10 citation statements)

References 24 publications

(46 reference statements)

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“…These enzymes use a pair of nucleosomes as their substrate and act as rulers to adjust the length of the linker DNA (27,40,41,58). Numerical simulations have confirmed their impact on internucleosome distances via examining the so-called radial distribution profile (46,50,59). The impact of these spacer enzymes on nucleosome density profiles near TSS remains unclear, however.…”

Section: Resultsmentioning

confidence: 99%

On the role of transcription in positioning nucleosomes

Jiang

Zhang

2020

Preprint

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Nucleosome positioning is crucial for the genome's function. Though the role of DNA sequence in positioning nucleosomes is well understood, a unified framework for studying the impact of transcription remains lacking. Using numerical simulations, we investigated the dependence of nucleosome density profiles on transcription level across multiple species. We found that the low nucleosome affinity of yeast, but not mouse, promoters contributes to the formation of phased nucleosomes arrays for inactive genes. For the active genes, a tug-of-war between two types of remodeling enzymes is essential for reproducing their density profiles. In particular, while ISW2 related enzymes are known to position the +1 nucleosome and align it toward the transcription start site (TSS), enzymes such as ISW1 that use a pair of nucleosomes as their substrate can shift the nucleosome array away from the TSS. Competition between these enzymes results in two types of nucleosome density profiles with well-and ill-positioned +1 nucleosome. Finally, we showed that Pol II assisted histone exchange, if occurring at a fast speed, can abolish the impact of remodeling enzymes. By elucidating the role of individual factors, our study reconciles the seemingly conflicting results on the overall impact of transcription in positioning nucleosomes across species.

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Section: Resultsmentioning

confidence: 99%

On the role of transcription in positioning nucleosomes

Jiang

Zhang

2020

Preprint

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“…Most of the theoretical approaches consider the DNA as a 1D lattice of units, which can adopt different states depending on reversible binding or covalent modifications (Chereji and Morozov, 2014;Vaillant et al, 2010;Schwab et al, 2008;Mobius et al, 2013;Morozov et al, 2009;Segal et al, 2006;Kaplan et al, 2009;Teif and Rippe, 2011;Teif and Rippe, 2010;Teif et al, 2010;Wang et al, 2008;Lubliner and Segal, 2009;Florescu et al, 2012;Teif and Rippe, 2009;Afek et al, 2011;Mirny, 2010;Gabdank et al, 2010;Chevereau et al, 2009;Reynolds et al, 2010). The size of the elementary lattice unit can be set either as one DNA base pair, or one nucleosome, or one can use an even larger coarse graining.…”

Section: Introductionmentioning

confidence: 99%

Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1) binding to nucleosomal arrays

Teif

Kepper

Yserentant

et al. 2015

J. Phys.: Condens. Matter

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Heterochromatin protein 1 (HP1) participates in establishing and maintaining heterochromatin via its histone-modification-dependent chromatin interactions. In recent papers HP1 binding to nucleosomal arrays was measured in vitro and interpreted in terms of nearest-neighbour cooperative binding. This mode of chromatin interaction could lead to the spreading of HP1 along the nucleosome chain. Here, we reanalysed previous data by representing the nucleosome chain as a 1D binding lattice and showed how the experimental HP1 binding isotherms can be explained by a simpler model without cooperative interactions between neighboring HP1 dimers. Based on these calculations and spatial models of dinucleosomes and nucleosome chains, we propose that binding stoichiometry depends on the nucleosome repeat length (NRL) rather than protein interactions between HP1 dimers. According to our calculations, more open nucleosome arrays with long DNA linkers are characterized by a larger number of binding sites in comparison to chains with a short NRL. Furthermore, we demonstrate by Monte Carlo simulations that the NRL dependent folding of the nucleosome chain can induce allosteric changes of HP1 binding sites. Thus, HP1 chromatin interactions can be modulated by the change of binding stoichiometry and the type of binding to condensed (methylated) and non-condensed (unmethylated) nucleosome arrays in the absence of direct interactions between HP1 dimers.

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“…The literature on nucleosome kinetics is dominated by nucleosome sliding 44 47 55 56 . However, our results suggest that nucleosome removal is the most important remodeling in the promoters.…”

Section: Discussionmentioning

confidence: 99%

Role of transcription factor-mediated nucleosome disassembly in PHO5 gene expression

Kharerin

Bhat

Marko³

et al. 2016

Sci Rep

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Studying nucleosome dynamics in promoter regions is crucial for understanding gene regulation. Nucleosomes regulate gene expression by sterically occluding transcription factors (TFs) and other non–histone proteins accessing genomic DNA. How the binding competition between nucleosomes and TFs leads to transcriptionally compatible promoter states is an open question. Here, we present a computational study of the nucleosome dynamics and organization in the promoter region of PHO5 gene in Saccharomyces cerevisiae. Introducing a model for nucleosome kinetics that takes into account ATP-dependent remodeling activity, DNA sequence effects, and kinetics of TFs (Pho4p), we compute the probability of obtaining different “promoter states” having different nucleosome configurations. Comparing our results with experimental data, we argue that the presence of local remodeling activity (LRA) as opposed to basal remodeling activity (BRA) is crucial in determining transcriptionally active promoter states. By modulating the LRA and Pho4p binding rate, we obtain different mRNA distributions—Poisson, bimodal, and long-tail. Through this work we explain many features of the PHO5 promoter such as sequence-dependent TF accessibility and the role of correlated dynamics between nucleosomes and TFs in opening/coverage of the TATA box. We also obtain possible ranges for TF binding rates and the magnitude of LRA.

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Kinetic Control of Nucleosome Displacement by ISWI/ACF Chromatin Remodelers

Cited by 18 publications

References 24 publications

On the role of transcription in positioning nucleosomes

On the role of transcription in positioning nucleosomes

Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1) binding to nucleosomal arrays

Role of transcription factor-mediated nucleosome disassembly in PHO5 gene expression

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