The inhibitor of histone acetyltransferases Nir regulates epidermis development

Abstract

Nir/ Noc2l is an inhibitor of histone acetyl-transferases (INHAT). In addition to its function on histone acetylation, Nir binds to p53 and TAp63 to regulate their activity. Here, we show that epidermis-specific ablation of Nir impairs epidermal stratification and barrier function, thereby causing perinatal lethality. Nir-deficient epidermis lacks appendages and remains single layered during embryogenesis. Cell proliferation is inhibited, whereas apoptosis and p53 acetylation is increased, indicating that Nir is controlling cell proliferation by limiting p53 acetylation. Transcriptome analysis revealed that Nir regulates expression of essential factors of epidermal development, such as keratins, integrins, and laminins. Furthermore, Nir binds to and controls expression of p63 and limits H3K18ac at the p63 promoter. Corroborating 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.