PLX263487

GSE139685: Functional interactions between Mi-2 and AP1 complexes control response and recovery from barrier disruption

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Keratinocytes respond to environmental signals by eliciting induction of genes that preserve skins 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-2 identified their striking convergence in mouse and human keratinocytes. Mi-2 directly repressed genes induced by barrier disruption by restricting AP1-enriched promoter-distal sites, occupied by Mi-2 and JUNB at steady state and by c-JUN after Mi-2 depletion or stress signaling. Barrier disruption led to a modest reduction in Mi-2 expression and a further selective reduction of Mi-2 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-2 did not prevent re-establishment of barrier integrity but was required for return to homeostasis. Thus a competition between Mi-2 repressive and activating AP1 complexes may permit rapid transcriptional response to and resolution from stress signaling. SOURCE: Katia Georgopoulos (katia.georgopoulos@cbrc2.mgh.harvard.edu) - Georgopoulos Harvard Medical School