In a new paper in Cell Research, Ji et al. find that transcription factor-instigated opening of chromatin, during cell reprogramming, can be sensed by the Baf60b-containing chromatin remodeling complex, which then activates the ATM-p53 pathway, leading to cell death. These findings from reprogramming studies unveil what I term a “chromatin remodeling checkpoint” whereby extensive, inappropriate chromatin opening events lead to cell elimination, thus preventing cell fate conversion that might occur upon tissue damage; if unchecked, such conversion could lead to metaplasia and cancer.