Transcriptional and Epigenetic Regulation of Cell Fate by YAP and TAZ.

Abstract

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) (YAP/TAZ) are key transcriptional coregulators that govern mammalian cell fate through complex epigenetic mechanisms. As core effectors of the Hippo signaling pathway, they integrate diverse cellular signals-including those mechanical, metabolic, or biochemical in nature-to control lineage specification, organ development, and tissue homeostasis. Although they have been traditionally known for their roles in the control of organ size and tumorigenesis, more recent evidence has revealed their function as important epigenetic modulators that reshape chromatin landscapes to direct cell fate transitions across multiple tissue contexts. Through interactions with chromatin-modifying complexes, the transcriptional machinery, and lineage-specific factors, YAP/TAZ coordinate enhancer activation, superenhancer formation, and chromatin looping to establish transcriptional programs essential for cellular identity. This work reviews the current understanding of YAP/TAZ-mediated epigenetic regulation and examines their tissue-specific roles. We propose a unified mechanistic framework by which the level of YAP/TAZ activity determines enhancer landscapes that favor either differentiated or progenitor-like cellular states, providing a potential basis for applications to regenerative medicine and therapeutic interventions.