The histone acetyltransferase inhibitor Nir regulates epidermis development

Development
Delphine DuteilRoland Schüle

Abstract

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 ofp63and limits H3K18ac at thep63promoter. 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.

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Citations

Jan 10, 2019·Experimental Dermatology·Sangjo KangTudorita Tumbar
Feb 2, 2021·OncoTargets and Therapy·Bolin ChenJiacai Wu
Feb 28, 2021·The Journal of Pathology·Zuzana PokornáPhilip J Coates

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