Abstract
Keratinocytes respond to environmental signals by eliciting induction of genes that preserve skin's integrity. Here we show that the transcriptional response to stress signaling is supported by short-lived epigenetic changes. Comparison of chromatin accessibility and transcriptional changes induced by barrier disruption or by loss of the nucleosome remodeler Mi-2β identified their striking convergence in mouse and human keratinocytes. Mi-2β directly repressed genes induced by barrier disruption by restricting AP1-enriched promoter-distal sites, occupied by Mi-2β and JUNB at steady state and by c-JUN after Mi-2β depletion or stress signaling. Barrier disruption led to a modest reduction in Mi-2β expression and a further selective reduction of Mi-2β localization at stress response genes, possibly through competition with activated c-JUN. Consistent with a repressive role at stress response genes, genetic ablation of Mi-2β did not prevent reestablishment of barrier integrity but was required for return to homeostasis. Thus, a competition between Mi-2β-repressive and activating AP1 complexes may permit rapid transcriptional response to and resolution from stress signaling.