There exists a hierarchy by which transcription factors can engage their target 
sites in chromatin, in that a subset of factors can bind transcriptionally 
silent, nucleosomal DNA, whereas most factors cannot, and this hierarchy is 
reflected, at least in part, in the developmental function of the factors. For 
example, transcription factors possessing the Forkhead box (Fox) DNA-binding 
domain contain an overall fold resembling that of linker histone and thus are 
structured to bind DNA, site specifically, in a nucleosomal context. Where 
tested, Fox factors bind early in the developmental or physiological activation 
of target genes, thereby enabling the binding of other factors that cannot 
engage chromatin on their own. To investigate the basis for early chromatin 
binding, we have used fluorescence recovery after photobleaching (FRAP) to 
analyze the mobility, in the live cell nucleus, of FoxA factors in comparison to 
linker histone and other transcription factors. We have further analyzed the 
factors for their ability to bind to chromatin in mitosis and thereby serve as 
epigenetic marks. The results indicate that the "pioneer" features of FoxA 
factors involve various chromatin-binding parameters seen in linker histones and 
that distinguish the factors with respect to their regulatory and mechanistic 
functions.