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The histone acetyltransferase inhibitor Nir regulates epidermis development.

Delphine Duteil1, Yves Tourrette1, Adrien Eberlin1

  • 1Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.

Development (Cambridge, England)
|March 2, 2018
PubMed
Summary

Nir (Noc2l) is crucial for skin development, regulating epidermal stratification and barrier function by controlling cell proliferation and mitotic spindle orientation. Its absence leads to severe developmental defects and perinatal lethality in mice.

Keywords:
EpidermisHistone acetylationMouse developmentNOC2-like nucleolar associated transcriptional repressorNovel INHAT repressorTrp53Trp63p63

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Dermatology

Background:

  • Nir (Noc2l) is known to inhibit histone acetyltransferases and interact with p53 and TAp63.
  • The precise role of Nir in epidermal development and skin homeostasis remains largely unexplored.

Purpose of the Study:

  • To investigate the function of Nir in epidermis-specific development.
  • To elucidate the molecular mechanisms by which Nir regulates skin formation and barrier function.

Main Methods:

  • Epidermis-specific Nir ablation in mice.
  • Histological analysis of skin structure and appendage formation.
  • Assessment of cell proliferation, apoptosis, and p53 acetylation.
  • Transcriptome analysis to identify regulated genes.
  • Analysis of mitotic spindle orientation and cell division.

Main Results:

  • Epidermis-specific Nir ablation resulted in impaired epidermal stratification and barrier function, leading to perinatal lethality.
  • Nir-deficient epidermis lacked appendages and remained single-layered, with inhibited cell proliferation and increased apoptosis and p53 acetylation.
  • Nir was found to regulate key epidermal development factors, including keratins, integrins, and laminins.
  • Nir controls p63 expression and limits histone acetylation at the p63 promoter, and is essential for asymmetric cell division and mitotic spindle orientation.

Conclusions:

  • Nir is a critical regulator of skin development, essential for epidermal stratification, barrier function, and appendage formation.
  • Nir controls cell proliferation and apoptosis by modulating p53 acetylation and regulates p63 expression, impacting epidermal development.
  • The findings highlight Nir's role in maintaining skin integrity and suggest its potential involvement in skin-related disorders.