MOF-mediated histone H4 Lysine 16 acetylation governs mitochondrial and ciliary functions by controlling gene

Dongmei Wang1,2, Haimin Li1, Navdeep S Chandel2,3

  • 1Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.

Nature Communications
|July 21, 2023
PubMed

Insights

The histone acetyltransferase MOF is crucial for skin development and function. Its absence impairs epithelial stem cell renewal, epidermal differentiation, and hair growth, leading to severe defects and lethality.

Area of Science:

  • Epigenetics
  • Developmental Biology
  • Molecular Biology

Background:

  • Histone H4 lysine 16 acetylation (H4K16ac) by MOF regulates gene expression.
  • The precise roles of MOF and H4K16ac in mammalian tissue development are not fully understood.

Purpose of the Study:

  • To investigate the function of MOF and H4K16ac in mammalian skin development and cellular processes.
  • To elucidate the molecular mechanisms underlying MOF-regulated skin development.

Main Methods:

  • Conditional deletion of Mof in mouse skin.
  • Analysis of epidermal differentiation and hair follicle growth.
  • Gene expression profiling of MOF-regulated genes.
  • Genetic deletion of Uqcrq in mouse skin.

Main Results:

  • Mof deletion in skin caused severe defects in progenitor self-renewal, epidermal differentiation, and hair follicle growth, leading to barrier defects and perinatal lethality.
  • MOF-regulated genes are enriched for mitochondrial and ciliary functions.
  • Deletion of Uqcrq, an electron transport chain Complex III subunit, mimicked MOF knockout phenotypes in skin.

Conclusions:

  • MOF-mediated epigenetic regulation is essential for mitochondrial and ciliary gene expression.
  • The MOF/electron transport chain axis plays a critical role in mammalian skin development.

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