How does Foxa transcription factor exhibits its pioneering function?
The conceptional framework of the mechanism of action of the FoxA proteins is that these 'pioneer factors' that can engage chromatin before other transcription factors. The Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stably. FoxA induces local DNA demethylation, nucleosome destabilization and binds to mitotic chromosomes. When associated with mitotic chromatin, FoxA may "bookmark" active genes and ensure their reactivation in postmitotic cells (epigenetic memory). About one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. The "pioneer" features of FoxA factors involve various chromatin-binding parameters seen in linker histones and distinguish the factors with respect to their regulatory and mechanistic functions.