| First Author | Shibata S | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 3 | PubMed ID | 31834931 |
| Mgi Jnum | J:289910 | Mgi Id | MGI:6432584 |
| Doi | 10.1084/jem.20182402 | Citation | Shibata S, et al. (2020) Functional interactions between Mi-2beta and AP1 complexes control response and recovery from skin barrier disruption. J Exp Med 217(3) |
| abstractText | 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. |
