The interplay of chromatin and transcription factors during cell fate transitions in development and reprogramming

Reprogramming to induced pluripotency through expression of OCT4, SOX2, KLF4, MYC (OSKM) factors is often considered the dedifferentiation of somatic cells. This would suggest that reprogramming represents the reversal of embryonic differentiation. Indeed, molecular events involving the activity of the pluripotency network occur in opposite directions. However, reprogramming and development substantially differ as OSKM bind to accessible regulatory elements in the genome of somatic cells due to their overexpression, including regulatory elements never bound by these factors during normal differentiation. In addition, rewiring the transcriptional network back to pluripotency involves overcoming molecular barriers that protect or stabilize the somatic identity, whereas extrinsic and intrinsic cues will drive differentiation in an energetically favorable landscape in the embryo. This review focuses on how cell fate transitions in reprogramming and development are differentially governed by interactions between transcription factors and chromatin. We also discuss how these interactions shape chromatin architecture and the transcriptional output. Major technological advances have resulted in a better understanding of both differentiation and reprogramming, which is essential to exploit reprogramming regimes for regenerative medicine.