Chromatin Scanning by Dynamic Binding of Pioneer Factors

Abstract

Pioneer factors such as FoxA target nucleosomal DNA and initiate cooperative interactions at silent genes during development, cellular reprogramming, and steroid hormone induction. Biophysical studies previously showed that the nuclear mobility of FoxA1 is slower than for many other transcription factors, whereas a new single molecule study (Swinstead et al., 2016, Cell) shows comparable chromatin residence times for FoxA1 and steroid receptors. Despite that steroid receptors engage nucleosome-remodeling complexes, the vast majority of co-bound sites with FoxA are dependent upon FoxA, not vice versa. Taken together, the distinguishing feature of pioneer factors remains nucleosomal access rather than an exceptional residence time in chromatin.

Figure. Chromatin scanning by pioneer factors

Chromatin across the bottom of the figure is depicted as consisting of open domains, naïve/unprogrammed domains, and repressed or heterochromatic domains. Pioneer factors (green blobs) are able to target the naïve domains, whereas non-pioneer factors (grey blobs) are typically dependent upon pioneers for binding there (black arrow). The green arrows depict transient, on-and-off association with chromatin as the factors scan the different domains; the red bars indicate the factors being impeded from scanning certain domains.