Figure 1

Opposing roles of histone H3.3 in reprogramming. (a) In somatic cells, pluripotency genes are in a repressive chromatin environment. Transient binding by a reprogramming factor to its binding site results in histone H3.3 incorporation, which in turn results in a more permissive chromatin structure and enhanced accessibility of the binding site. These chromatin changes increase the probability of concomitant binding of Oct4, Sox2 and Klf4 and activation of the target pluripotency gene. (b) Active genes are marked by high levels of histone H3.3. During DNA replication H3.3 is diluted out by the replication-dependent incorporation of histone H3.1. Depending on appropriate cues the gene will either become re-activated or become silenced. During reprogramming, tissue-specific genes become progressively silenced. High levels of H3.3 expression, however, increase the probability of H3.3 incorporation and therefore promote the memory of the somatic cell gene expression pattern.