Fiche publication
Date publication
mars 2018
Journal
Development (Cambridge, England)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DUTEIL Delphine
Tous les auteurs :
Duteil D, Tourrette Y, Eberlin A, Willmann D, Patel D, Friedrichs N, Müller JM, Schüle R
Lien Pubmed
Résumé
In addition to its function as an inhibitor of histone acetyltransferases, Nir (Noc2l) binds to p53 and TAp63 to regulate their activity. Here, we show that epidermis-specific ablation of Nir impairs epidermal stratification and barrier function, resulting in perinatal lethality. Nir-deficient epidermis lacks appendages and remains single layered during embryogenesis. Cell proliferation is inhibited, whereas apoptosis and p53 acetylation are increased, indicating that Nir is controlling cell proliferation by limiting p53 acetylation. Transcriptome analysis revealed that Nir regulates the expression of essential factors in epidermis development, such as keratins, integrins and laminins. Furthermore, Nir binds to and controls the expression of and limits H3K18ac at the promoter. Corroborating the stratification defects, asymmetric cell divisions were virtually absent in Nir-deficient mice, suggesting that Nir is required for correct mitotic spindle orientation. In summary, our data define Nir as a key regulator of skin development.
Mots clés
Epidermis, Histone acetylation, Mouse development, NOC2-like nucleolar associated transcriptional repressor, Novel INHAT repressor, Trp53, Trp63, p63
Référence
Development. 2018 03 21;145(6):
