Epigenetic Mechanisms of Pituitary Cell Fate Specification

Pituitary progenitor or stem cells present in the pituitary primordium during development are the source of hormone-producing cells of the adult pituitary. These stem cells are maintained in the adult tissue and they can be recruited to maintain or replenish differentiated pituitary cells. We currently have only limited insight into the mechanisms that trigger progenitor engagement into one or the other pituitary differentiation pathway. While transcription factors that drive terminal differentiation have been identified for different lineages, current evidence suggests that initial engagement of progenitors into differentiation may be due to earlier-acting factors. One such factor expressed at the transition between progenitor and differentiated state was identified in the intermediate lobe; this factor, Pax7, exerts its action through a pioneer factor activity. Pioneer transcription factors have the unique ability to bind target sequences in compacted chromatin and to initiate chromatin “opening” for recruitment of other transcription factors. Pax7 accomplishes this process on about 2500 enhancers genome-wide, allowing for Tpit recruitment at a subset for implementation of the melanotrope-specific program of gene expression. Current knowledge about this process is reviewed here, together with a discussion of future challenges in order to understand the unique properties of pioneer transcription factor action and cell reprogramming through chromatin remodelling.