FOXD3 controls pluripotency through modulating enhancer activity

Pluripotent stem cell governs the potential for full and proper range of early development. These cell fate transitions are mostly achieved by the sequential binding of transcription factors (TFs) and the associated changes in gene expression. Enhancers are the major DNA elements that are involved in the regulation of cell-specific gene expression. Thus, to understand the drivers of these transitions and the exact mechanisms for these cells to retain their pluripotency, it is essential to look deeper into these enhancers and how they work with various TFs. Krishnakumar et al. recently identified that forkhead TF FOXD3 binds to a differential set of enhancers in embryonic stem cells (ESCs) and epiblast cells (EpiCs). FOXD3 acts as a pioneer TF and precedes the binding of other TFs to regulate gene expression by the regulation of local chromatin structure and nucleosomes. Notably, FOXD3 interacts with both the SW1/SNF chromatin remodelling complex ATPase BRG1 and histone deacetylase 1/2 (HDAC1/2), in order to keep expression in check by activating and simultaneously suppressing different sets of genes.