Functional interactions between Mi-2β and AP1 complexes control response and recovery from skin barrier disruption.

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-2beta identified their striking convergence in mouse and human keratinocytes. Mi-2beta directly repressed genes induced by barrier disruption by restricting AP1-enriched promoter-distal sites, occupied by Mi-2beta and JUNB at steady state and by c-JUN after Mi-2beta depletion or stress signaling. Barrier disruption led to a modest reduction in Mi-2beta expression and a further selective reduction of Mi-2beta 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-2beta did not prevent reestablishment of barrier integrity but was required for return to homeostasis. Thus, a competition between Mi-2beta-repressive and activating AP1 complexes may permit rapid transcriptional response to and resolution from stress signaling.