PRDM14 and melanoma: We show that stress exerted on microconfined cells at the periphery primes the melanoma phenotype through epigenetic reprogramming via histone modifications H3K9ac and H3K4me2, and involvement of the epigenetic modifier PRDM14. While we have shown how geometric cues can give rise to differential activity of PRDM14, it remains to be demonstrated how PRDM14 is activated based on these biophysical inputs.