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Phys Biol. 2011 Aug;8(4):044001. doi: 10.1088/1478-3975/8/4/044001. Epub 2011 Jun 10.

Nucleosome mediated crosstalk between transcription factors at eukaryotic enhancers.

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BioQuant and German Cancer Research Center, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.


A recent study of transcription regulation in Drosophila embryonic development revealed a complex non-monotonic dependence of gene expression on the distance between binding sites of repressor and activator proteins at the corresponding enhancer cis-regulatory modules (Fakhouri et al 2010 Mol. Syst. Biol. 6 341). The repressor efficiency was high at small separations, low around 30 bp, reached a maximum at 50-60 bp, and decreased at larger distances to the activator binding sites. Here, we propose a straightforward explanation for the distance dependence of repressor activity by considering the effect of the presence of a nucleosome. Using a method that considers partial unwrapping of nucleosomal DNA from the histone octamer core, we calculated the dependence of activator binding on the repressor-activator distance and found a quantitative agreement with the distance dependence reported for the Drosophila enhancer element. In addition, the proposed model offers explanations for other distance-dependent effects at eukaryotic enhancers.

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