Grhl3 coordinates epithelial gene activation and epigenetic remodeling in fibroblasts

The mesenchymal-to-epithelial transition (MET) is a critical and stepwise process in cellular reprogramming and development. Grhl3 has been implicated in MET, but its capacity to initiate epithelial programs in non-epithelial cells remains incompletely defined. Here, we demonstrate that Grhl3 overexpression in MEFs induces a transcriptional shift consistent with early MET, characterized by activation of epithelial genes and suppression of mesenchymal features. This response is accompanied by chromatin changes indicative of gene activation at epithelial loci and is reinforced through cooperative interactions with other MET-associated transcription factors. Grhl3 is associated with locus-specific changes in DNA methylation and with regulatory engagement at genes involved in epigenetic maintenance. Together, these findings position Grhl3 as a central coordinator of epithelial gene activation and epigenetic remodeling in a non-epithelial context, supporting its role in initiating early, transcriptionally and epigenetically primed MET states.