2A-DUB/Mysm1 Regulates Epidermal Development in Part by Suppressing p53-Mediated Programs

Language
en
Document Type
Article
Issue Date
2022-10-20
First published
2018-02-28
Issue Year
2022
Authors
Wilms, Christina
Krikki, Ioanna
Hainzl, Adelheid
Kilo, Sonja
Alupei, Marius
Makrantonaki, Evgenia
Wagner, Maximilian
Kroeger, Carsten
Brinker, Titus
Gatzka, Martina
Editor
Publisher
MDPI
Abstract

Development and homeostasis of the epidermis are governed by a complex network of sequence-specific transcription factors and epigenetic modifiers cooperatively regulating the subtle balance of progenitor cell self-renewal and terminal differentiation. To investigate the role of histone H2A deubiquitinase 2A-DUB/Mysm1 in the skin, we systematically analyzed expression, developmental functions, and potential interactions of this epigenetic regulator using Mysm1-deficient mice and skin-derived epidermal cells. Morphologically, skin of newborn and young adult Mysm1-deficient mice was atrophic with reduced thickness and cellularity of epidermis, dermis, and subcutis, in context with altered barrier function. Skin atrophy correlated with reduced proliferation rates in Mysm1−/− epidermis and hair follicles, and increased apoptosis compared with wild-type controls, along with increases in DNA-damage marker γH2AX. In accordance with diminished α6-Integrinhigh+CD34+ epidermal stem cells, reduced colony formation of Mysm1−/− epidermal progenitors was detectable in vitro. On the molecular level, we identified p53 as potential mediator of the defective Mysm1-deficient epidermal compartment, resulting in increased pro-apoptotic and anti-proliferative gene expression. In Mysm1−/−p53−/− double-deficient mice, significant recovery of skin atrophy was observed. Functional properties of Mysm1−/− developing epidermis were assessed by quantifying the transepidermal water loss. In summary, this investigation uncovers a role for 2A-DUB/Mysm1 in suppression of p53-mediated inhibitory programs during epidermal development.

Journal Title
International Journal of Molecular Sciences
Volume
19
Issue
3
Citation

International Journal of Molecular Sciences 19.3 (2018): 687. https://www.mdpi.com/1422-0067/19/3/687

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