Dynamic Morphogen-p63 Chromatin Interactions That Guide Epigenetic Changes and p63 Activity in Surface Ectoderm Commitment

The study explored how the transcription factor p63 influences the differentiation of skin cells, specifically the commitment of surface ectoderm cells. Using an in vitro differentiation protocol with retinoic acid and bone morphogenetic protein, and manipulating p63 expression in stem cells, the researchers applied various genomic techniques to examine transcriptional and chromatin changes. They discovered that p63 requires morphogenetic signals to affect gene expression, as its overexpression alone was insufficient. Morphogens altered the chromatin landscape, allowing p63 to regulate genes effectively, with chromatin looping playing a role in gene expression changes. Additionally, the deletion of a distal cis-regulatory element that controls TFAP2C, a crucial developmental regulator, led to its deregulation and the disruption of its feedback loop with p63. These results shed light on the intricate interactions between morphogens and p63, which are vital for skin cell differentiation and could enhance stem cell treatments for skin diseases like epidermolysis bullosa.