Several mechanisms have been proposed to explain this phenomenon, including protein-protein interactions that enable ternary complex formation with DNA (Verger and Duterque-Coquillaud, 2002), pioneering factors that disrupt the closed nucleosome conformation and enable other factors to bind (Cirillo et al., 2002), cooperative binding of one or more factors to clustered sites that facilitates nucleosome displacement and stable binding of the factors involved (Boyes and Felsenfeld, 1996; Miller and Widom, 2003), and binding to chromatin marked in a cell type-specific manner by lysine 4-methylated histone H3 (H3K4me1/2) (Lupien et al., 2008), a sign of open chromatin that is correlated with activity of nearby genes (Heintzman et al., 2009). However, how transcription factors gain access to their eventual binding sites and the hierarchy of events that generate their cell type-specific binding and the associated epigenetic modification patterns have not previously been elucidated on a genome-wide scale.
