Dataset Information

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

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-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 reestablishment 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.

SUBMITTER: Shibata S

PROVIDER: S-EPMC7062528 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Shibata Sayaka S Kashiwagi Mariko M Morgan Bruce A BA Georgopoulos Katia K

The Journal of experimental medicine 20200301 3

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 ...[more]

PMID: 31834931

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Project description:ObjectivesIn the setting of reperfused acute myocardial infarction (AMI), the authors sought to compare prediction of contractile recovery by infarct extracellular volume (ECV), as measured by T1-mapping cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) transmural extent.BackgroundThe transmural extent of myocardial infarction as assessed by LGE CMR is a strong predictor of functional recovery, but accuracy of the technique may be reduced in AMI. ECV mapping by CMR can provide a continuous measure associated with the severity of tissue damage within infarcted myocardium.MethodsThirty-nine patients underwent acute (day 2) and convalescent (3 months) CMR scans following AMI. Cine imaging, tissue tagging, T2-weighted imaging, modified Look-Locker inversion T1 mapping natively and 15 min post-gadolinium-contrast administration, and LGE imaging were performed. The ability of acute infarct ECV and acute transmural extent of LGE to predict convalescent wall motion, ejection fraction (EF), and strain were compared per-segment and per-patient.ResultsPer-segment, acute ECV and LGE transmural extent were associated with convalescent wall motion score (p < 0.01; p < 0.01, respectively). ECV had higher accuracy than LGE extent to predict improved wall motion (area under receiver-operating characteristics curve 0.77 vs. 0.66; p = 0.02). Infarct ECV ≤0.5 had sensitivity 81% and specificity 65% for prediction of improvement in segmental function; LGE transmural extent ≤0.5 had sensitivity 61% and specificity 71%. Per-patient, ECV and LGE correlated with convalescent wall motion score (r = 0.45; p < 0.01; r = 0.41; p = 0.02, respectively) and convalescent EF (p < 0.01; p = 0.04). ECV and LGE extent were not significantly correlated (r = 0.34; p = 0.07). In multivariable linear regression analysis, acute infarct ECV was independently associated with convalescent infarct strain and EF (p = 0.03; p = 0.04), whereas LGE was not (p = 0.29; p = 0.24).ConclusionsAcute infarct ECV in reperfused AMI can complement LGE assessment as an additional predictor of regional and global LV functional recovery that is independent of transmural extent of infarction.

Dataset Information

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

Publications

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

Similar Datasets

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