The histone acetyltransferase inhibitor Nir regulates epidermis development

Delphine Duteil, Yves Tourrette, Adrien Eberlin, Dominica Willmann, Dharmeshkumar Patel, Nicolaus Friedrichs, Judith M. Müller, Roland Schüle

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 of p63 and limits H3K18ac at the p63 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.

Original languageEnglish (US)
Article numberdev158543
JournalDevelopment (Cambridge)
Volume145
Issue number6
DOIs
StatePublished - Mar 2018

Bibliographical note

Funding Information:
This work was supported by grants of the European Research Council (AdGrant 322844 to R.S.) and the Deutsche Forschungsgemeinschaft (SFB 992, SFB 850 and SFB 746 to R.S.).

Publisher Copyright:
© 2018. Published by The Company of Biologists Ltd.

Keywords

  • Epidermis
  • Histone acetylation
  • Mouse development
  • NOC2-like nucleolar associated transcriptional repressor
  • Novel INHAT repressor
  • P63
  • Trp53
  • Trp63

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