Pioneer transcription factors, chromatin dynamics, and cell fate control

Abstract

Among the diverse transcription factors that are necessary to elicit changes in cell fate, both in embryonic development and in cellular reprogramming, a subset of factors are capable of binding to their target sequences on nucleosomal DNA and initiating regulatory events in silent chromatin. Such 'pioneer transcription factors' initiate cooperative interactions with other regulatory proteins to elicit changes in local chromatin structure. As a consequence of pioneer factor binding, the local chromatin can either become open and competent for activation, closed and repressed, or transcriptionally active. Understanding how pioneer factors initiate chromatin dynamics and how such can be blocked at heterochromatic sites provides insights into controlling cell fate transitions at will.

Figure 1. Activities of pioneer factors

(top) Pioneer factors can scan nucleosomal DNA for their target sites in silent chromatin. (middle) Increased residence time at targeted sites allows for cooperative interactions with other factors and more stable binding. (bottom) Binding of pioneer factors can lead to activated sequences (left) with open chromatin features (green flags) and a state of competence to be expressed or direct transcriptional activity, or repressed sequences (right) with closed chromatin features (red flags).