In eukaryotes, DNA-binding of many protein factors involved in processes like transcription, replication, repair and recombination is dependent on the chromatin organization. In particular the wrapping of DNA around the histone octamer complex has long been recognized as a mechanism to make DNA sequences inaccessible for the binding of other proteins. Accordingly, changes of nucleosome positions at promoter and enhancer regions have been shown to directly affect gene expression. Nucleosome positions are determined by three major contributions: the intrinsic binding affinity of the histone octamer depends on the DNA sequence, competitive/cooperative binding of other protein factors, and active translocation by ATP-dependent remodeling complexes. The challenge is to take into accout all these contributions and predict nucleosome repositioning in gene regulation in vivo (Teif & Rippe, NAR 2009; Teif & Rippe, JPCM 2010). Importantly, the possibility of TFs to access the DNA inside nucleosomes should be also taken into account (Teif et al. BJ 2010) because it dramatically affects input-output functions of eukaryotic enhancers (Teif and Rippe, 2011).