Programmable genetic switches to control transcriptional machinery of pluripotency

Transcriptional activators play a central role in the regulation of gene expression and have the ability to manipulate the specification of cell fate. Pluripotency is a transient state where a cell has the potential to develop into more than one type of mature cell. The induction of pluripotency in differentiated cells requires extensive chromatin reorganization regulated by core transcriptional machinery. Several small molecules have been shown to enhance the efficiency of somatic cell reprogramming into pluripotent stem cells. However, entirely chemical-based reprogramming remains elusive. Recently, we reported that selective DNA-binding hairpin pyrrole-imidazole polyamides conjugated with histone deacetylase inhibitor could mimic natural transcription factors and epigenetically activate certain pluripotency-associated genes. Here, we review the need to develop selective chromatin-modifying transcriptional activators for somatic genome reprogramming.