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

Wilms C, Krikki I, Hainzl A, Kilo S, Alupei M, Makrantonaki E, Wagner M, Kroeger CM, Brinker TJ, Gatzka M (2018)

Publication Type: Journal article

Publication year: 2018


Book Volume: 19

Journal Issue: 3

DOI: 10.3390/ijms19030687


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.

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Wilms, C., Krikki, I., Hainzl, A., Kilo, S., Alupei, M., Makrantonaki, E.,... Gatzka, M. (2018). 2A-DUB/Mysm1 Regulates Epidermal Development in Part by Suppressing p53-Mediated Programs. International Journal of Molecular Sciences, 19(3). https://dx.doi.org/10.3390/ijms19030687


Wilms, Christina, et al. "2A-DUB/Mysm1 Regulates Epidermal Development in Part by Suppressing p53-Mediated Programs." International Journal of Molecular Sciences 19.3 (2018).

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