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Quantitative models for accelerated protein dissociation from nucleosomal DNA.

Chen C, Bundschuh R - Nucleic Acids Res. (2014)

Bottom Line: This reduces the rate of transcription factor binding and is a known mechanism for regulation of gene expression via chromatin structure.There are two possible explanations for such an increase in off-rate short of an active role of the nucleosome in pushing the transcription factor off the DNA: (i) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (ii) the nucleosome can change the equilibrium between specific and non-specific binding to the DNA.We explicitly model both scenarios and find that dimeric binding can explain a large increase in off-rate while the non-specific binding model cannot be reconciled with the large, experimentally observed increase.

View Article: PubMed Central - PubMed

Affiliation: Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA Center for RNA Biology, The Ohio State University, Columbus, OH, USA.

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The overall off rate of LexA dissociation from a nucleosome compared to naked DNA for the non-specific binding model. The overall off rate of LexA in the presence of a nucleosome for 35 combinations of the unknown parameters K and k1 covering the entire range of biologically plausible values is calculated and presented as a fold change compared to the naked DNA case.
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Figure 4: The overall off rate of LexA dissociation from a nucleosome compared to naked DNA for the non-specific binding model. The overall off rate of LexA in the presence of a nucleosome for 35 combinations of the unknown parameters K and k1 covering the entire range of biologically plausible values is calculated and presented as a fold change compared to the naked DNA case.

Mentions: Again, we use the measured overall off rate of TF dissociation from naked DNA to determine the unknown parameters and thus have to limit ourselves to the case of LexA. Since several parameters are unknown, we vary their values within experimentally reasonable values. The parameters we vary are the ratio K = Kd(non-specific binding) /Kd(specific binding) and sliding rate k1 because all other parameters can be obtained based on these two. We varied K from 100 to 100,000 based on experimental estimates of this number (28), and varied k1 from 103 s−1 to 107 s−1 to cover the range of sliding rates of many known DNA-binding proteins (29). We investigated all combinations of K and k1 resulting in 35 different conditions (Figure 4).


Quantitative models for accelerated protein dissociation from nucleosomal DNA.

Chen C, Bundschuh R - Nucleic Acids Res. (2014)

The overall off rate of LexA dissociation from a nucleosome compared to naked DNA for the non-specific binding model. The overall off rate of LexA in the presence of a nucleosome for 35 combinations of the unknown parameters K and k1 covering the entire range of biologically plausible values is calculated and presented as a fold change compared to the naked DNA case.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4150810&req=5

Figure 4: The overall off rate of LexA dissociation from a nucleosome compared to naked DNA for the non-specific binding model. The overall off rate of LexA in the presence of a nucleosome for 35 combinations of the unknown parameters K and k1 covering the entire range of biologically plausible values is calculated and presented as a fold change compared to the naked DNA case.
Mentions: Again, we use the measured overall off rate of TF dissociation from naked DNA to determine the unknown parameters and thus have to limit ourselves to the case of LexA. Since several parameters are unknown, we vary their values within experimentally reasonable values. The parameters we vary are the ratio K = Kd(non-specific binding) /Kd(specific binding) and sliding rate k1 because all other parameters can be obtained based on these two. We varied K from 100 to 100,000 based on experimental estimates of this number (28), and varied k1 from 103 s−1 to 107 s−1 to cover the range of sliding rates of many known DNA-binding proteins (29). We investigated all combinations of K and k1 resulting in 35 different conditions (Figure 4).

Bottom Line: This reduces the rate of transcription factor binding and is a known mechanism for regulation of gene expression via chromatin structure.There are two possible explanations for such an increase in off-rate short of an active role of the nucleosome in pushing the transcription factor off the DNA: (i) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (ii) the nucleosome can change the equilibrium between specific and non-specific binding to the DNA.We explicitly model both scenarios and find that dimeric binding can explain a large increase in off-rate while the non-specific binding model cannot be reconciled with the large, experimentally observed increase.

View Article: PubMed Central - PubMed

Affiliation: Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA Center for RNA Biology, The Ohio State University, Columbus, OH, USA.

Show MeSH
Related in: MedlinePlus