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

International Journal of Molecular Sciences
Christina WilmsMartina Gatzka

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-pro...Continue Reading

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Citations

May 30, 2020·International Journal of Molecular Sciences·Carsten KroegerMartina Vanessa Gatzka
Apr 30, 2020·International Journal of Molecular Sciences·Amanda FioreAnastasia Nijnik
Aug 27, 2019·Biochimica Et Biophysica Acta. Reviews on Cancer·Ji ChengWenyi Wei
Mar 30, 2021·EMBO Reports·Kevin G Mark, Michael Rape
Aug 7, 2021·Journal of Cosmetic Dermatology·Jianbiao HeYan Jia

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Methods Mentioned

BETA
deubiquitination
fluorescence-activated cell sorting
Assay

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