title: Nucleosome mediated crosstalk between transcription factors at eukaryotic enhancers.
abstract: 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.
authors.affiliation: BioQuant and German Cancer Research Center, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany. Vladimir.Teif@bioquant.uni-heidelberg.de
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Teif
authors.forename: Karsten
authors.initials: K
authors.lastname: Rippe
mesh_terms: D000818:Animals; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D009707:Nucleosomes; D012097:Repressor Proteins; D014157:Transcription Factors