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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
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.
Abstract:
Histone H4 lysine 16 acetylation (H4K16ac), governed by the histone acetyltransferase MOF, orchestrates gene expression regulation and chromatin interaction. However, the roles of MOF and H4K16ac in controlling cellular function and regulating mammalian tissue development remain unclear. Here we show that conditional deletion of Mof in the skin, but not Kansl1, causes severe defects in the self-renewal of basal epithelial progenitors, epidermal differentiation, and hair follicle growth, resulting in barrier defects and perinatal lethality. MOF-regulated genes are highly enriched for essential functions in the mitochondria and cilia. Genetic deletion of Uqcrq, an essential subunit for the electron transport chain (ETC) Complex III, in the skin, recapitulates the defects in epidermal differentiation and hair follicle growth observed in MOF knockout mouse. Together, this study reveals the requirement of MOF-mediated epigenetic mechanism for regulating mitochondrial and ciliary gene expression and underscores the important function of the MOF/ETC axis for mammalian skin development.
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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