Canoes, camels, cars and catamarans have carried human pioneers far and wide; taking us to undiscovered lands to encounter unseen beauty, encouraged by the hope of fame, glory, and a lust for adventure. How pioneer transcription factors brave the inhospitable exterior of a compacted DNA-histone complex to induce transcription of tightly guarded genes is, however, relatively unknown. This is an especially tantalizing phenomenon in the context of the reprogramming of somatic cells to pluripotent stem cells via the forced expression of Oct4, Sox2, Klf4, and Myc.
A new study from the laboratory of Kenneth S. Zaret hoped to understand how these factors initiate transcription of the silenced pluripotency gene network, and his team discovered that all they needed was a little “wiggle”. They discovered that:
- Oct4, Sox2, and Klf4 display independent binding affinities, employing both specific and non-specific chromatin interactions.
- This non-specific “wiggle” factor imbues them with their pioneering character, allowing them to bind partial/degenerate binding sites in silent chromatin loci.
- Myc cannot bind to nucleosomes in this manner, and so is not so adventurous!
- But Oct4, Sox2, and Klf4 synergize with c-Myc to aid binding to target partial binding sites.
The authors suggest that this wiggle and cooperative functions imbue these transcription factors with their pioneer capabilities, further enhancing our mechanistic understanding of the initiation of the process of reprogramming to create pluripotent stem cells. The authors also suggest that the application of this knowledge may also improve other reprogramming strategies, perhaps leading to the ability to easily and efficiently alter cell fates.
So get a wiggle on and head on over to read this adventurous study in Cell, 2015.