2A-DUB/Mysm1 regulates epidermal development in part by suppressing p53-mediated programs

• Verfasst von: Wilms, Christina [VerfasserIn]
• Verfasst von: Brinker, Titus Josef [VerfasserIn]
• Titel: 2A-DUB/Mysm1 regulates epidermal development in part by suppressing p53-mediated programs
• Verf.angabe: Christina Wilms, Ioanna Krikki, Adelheid Hainzl, Sonja Kilo, Marius Alupei, Evgenia Makrantonaki, Maximilian Wagner, Carsten M. Kroeger, Titus Josef Brinker and Martina Gatzka
• E-Jahr: 2018
• Jahr: 28 February 2018
• Umfang: 12 S.
• Fussnoten: Gesehen am 26.03.2020
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2018
• Band/Heft Quelle: 19(2018,3) Artikel-Nummer 687, 12 Seiten
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms19030687
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: apoptosis
• Sach-SW: DUB
• Sach-SW: epidermal barrier
• Sach-SW: epidermal stem cell
• Sach-SW: epigenetics
• Sach-SW: histone modification
• Sach-SW: Mysm1
• Sach-SW: p53
• Sach-SW: p63
• Sach-SW: skin
• K10plus-PPN: 1693339269

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.