Role of Nucleosome Sliding in the Protein Target Search for Covered DNA Sites

Associations of transcription factors (TFs) with specific sites on DNA initiate major cellular processes. But DNA in eukaryotic cells is covered by nucleosomes which prevent TFs from binding. However, nucleosome structures on DNA are not static and exhibit breathing and sliding. We develop a theoretical framework to investigate the effect of nucleosome sliding on a protein target search. By analysis of a discrete-state stochastic model of nucleosome sliding, search dynamics are explicitly evaluated. It is found that for long sliding lengths the target search dynamics are faster for normal TFs that cannot enter the nucleosomal DNA. But for more realistic short sliding lengths, the so-called pioneer TFs, which can invade nucleosomal DNA, locate specific sites faster. It is also suggested that nucleosome breathing, which is a faster process, has a stronger effect on protein search dynamics than that of nucleosome sliding. Theoretical arguments to explain these observations are presented.